A mammalian neuropeptide of 10 amino acids that belongs to the tachykinin family. It is similar in structure and action to SUBSTANCE P and NEUROKININ B with the ability to excite neurons, dilate blood vessels, and contract smooth muscles, such as those in the BRONCHI.
A mammalian neuropeptide of 10 amino acids that belongs to the tachykinin family. It is similar in structure and action to SUBSTANCE P and NEUROKININ A with the ability to excite neurons, dilate blood vessels, and contract smooth muscles, such as those in the URINARY BLADDER and UTERUS.
A class of cell surface receptors for tachykinins that prefers neurokinin A; (NKA, substance K, neurokinin alpha, neuromedin L), neuropeptide K; (NPK); or neuropeptide gamma over other tachykinins. Neurokinin-2 (NK-2) receptors have been cloned and are similar to other G-protein coupled receptors.
A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells.
A family of biologically active peptides sharing a common conserved C-terminal sequence, -Phe-X-Gly-Leu-Met-NH2, where X is either an aromatic or a branched aliphatic amino acid. Members of this family have been found in mammals, amphibians, and mollusks. Tachykinins have diverse pharmacological actions in the central nervous system and the cardiovascular, genitourinary, respiratory, and gastrointestinal systems, as well as in glandular tissues. This diversity of activity is due to the existence of three or more subtypes of tachykinin receptors.
A class of cell surface receptors for tachykinins that prefers neurokinin B (neurokinin beta, neuromedin K) over other tachykinins. Neurokinin-3 (NK-3) receptors have been cloned and are members of the G-protein coupled receptor superfamily. They have been found in the central nervous system and in peripheral tissues.
An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.
Cell surface proteins that bind TACHYKININS with high affinity and trigger intracellular changes influencing the behavior of cells. Three classes of tachykinin receptors have been characterized, the NK-1; NK-2; and NK-3; which prefer, respectively, SUBSTANCE P; NEUROKININ A; and NEUROKININ B.
Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.
Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.
Intercellular signaling peptides that were originally characterized by their ability to suppress NEOPLASM METASTASIS. Kisspeptins have since been found to play an important role in the neuroendocrine regulation of REPRODUCTION.
A peptide extracted from the posterior salivary glands of certain small octopi (Eledone spp., Mollusca), or obtained by synthesis. Its actions resemble those of SUBSTANCE P; it is a potent vasodilator and increases capillary permeability. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1364)
Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.
An oligopeptide isolated from the skin of Physalaemus fuscumaculatus, a South American frog. It is a typical kinin, resembling SUBSTANCE P in structure and action and has been proposed as a sialagogue, antihypertensive, and vasodilator.
Quinuclidines are organic compounds consisting of a tricyclic structure with a three-membered ring fused to a piperidine ring, often used as building blocks in the synthesis of pharmaceuticals and bioactive molecules.
An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.
A cyclized derivative of L-GLUTAMIC ACID. Elevated blood levels may be associated with problems of GLUTAMINE or GLUTATHIONE metabolism.
A family of hexahydropyridines.
A nucleus located in the middle hypothalamus in the most ventral part of the third ventricle near the entrance of the infundibular recess. Its small cells are in close contact with the ependyma.
A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.
Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
Narrowing of the caliber of the BRONCHI, physiologically or as a result of pharmacological intervention.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.
A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.
BENZOIC ACID amides.
An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.
The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.
Inflammation caused by an injurious stimulus of peripheral neurons and resulting in release of neuropeptides which affect vascular permeability and help initiate proinflammatory and immune reactions at the site of injury.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.
A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.
A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.
Use of electric potential or currents to elicit biological responses.
Biphenyl compounds are organic substances consisting of two phenyl rings connected by a single covalent bond, and can exhibit various properties and uses, including as intermediates in chemical synthesis, components in plastics and dyes, and as additives in fuels.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Bethanechol compounds are parasympathomimetic agents that directly stimulate muscarinic receptors, primarily used to treat urinary retention and nonobstructive bladder dysfunction by increasing bladder contractility and decreasing post-void residual volume.
Neurons in the SPINAL CORD DORSAL HORN whose cell bodies and processes are confined entirely to the CENTRAL NERVOUS SYSTEM. They receive collateral or direct terminations of dorsal root fibers. They send their axons either directly to ANTERIOR HORN CELLS or to the WHITE MATTER ascending and descending longitudinal fibers.
The flattened, funnel-shaped expansion connecting the URETER to the KIDNEY CALICES.
A slowly hydrolyzing muscarinic agonist with no nicotinic effects. Bethanechol is generally used to increase smooth muscle tone, as in the GI tract following abdominal surgery or in urinary retention in the absence of obstruction. It may cause hypotension, HEART RATE changes, and BRONCHIAL SPASM.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
Protein precursors, also known as proproteins or prohormones, are inactive forms of proteins that undergo post-translational modification, such as cleavage, to produce the active functional protein or peptide hormone.

Two affinities for a single antagonist at the neuronal NK1 tachykinin receptor: evidence from quantitation of receptor endocytosis. (1/828)

1. In smooth muscle contractility assays, many NK1 receptor (NK1r) antagonists inhibit responses to the neurotransmitter, substance P (SP), and its analogue, septide, with markedly different potency, leading to the proposal that there is a septide-preferring receptor related to the NK1r. 2. We used fluorescence immunohistochemistry and confocal microscopy to visualize agonist-induced NK1r endocytosis and analyse agonist/antagonist interactions at native NK1r in neurons of the myenteric plexus of guinea-pig ileum. 3. SP and septide gave sigmoid log concentration-response curves and were equipotent in inducing NK1r endocytosis. 4. The NK1r antagonists, CP-99994 (2S,3S)-3-(2-methoxybenzyl)amino-2-phenylpiperidine dihydrochloride and MEN-10581, cyclo(Leu,[CH2NH]Lys(benzyloxycarbonyl)-Gln-Trp-Phe-betaAla) were both more potent in inhibiting endocytosis (50 x and 8 x greater respectively) against septide than against SP. 5. The results suggest that SP and septide interact differently with the NK1r, and that a single antagonist can exhibit different affinities at a single NK1r population, depending on the agonist with which it competes. Thus it may not be necessary to posit a separate septide-preferring tachykinin receptor.  (+info)

The distribution of neurons expressing calcium-permeable AMPA receptors in the superficial laminae of the spinal cord dorsal horn. (2/828)

The superficial dorsal horn is a major site of termination of nociceptive primary afferents. Fast excitatory synaptic transmission in this region is mediated mainly by release of glutamate onto postsynaptic AMPA and NMDA receptors. NMDA receptors are known to be Ca2+-permeable and to provide synaptically localized Ca2+ signals that mediate short-term and long-term changes in synaptic strength. Less well known is a subpopulation of AMPA receptors that is Ca2+-permeable and has been shown to be synaptically localized on dorsal horn neurons in culture (Gu et al., 1996) and expressed by dorsal horn neurons in situ (Nagy et al., 1994; Engelman et al., 1997). We used kainate-induced cobalt uptake as a functional marker of neurons expressing Ca2+-permeable AMPA receptors and combined this with markers of nociceptive primary afferents in the postnatal rat dorsal horn. We have shown that cobalt-positive neurons are located in lamina I and outer lamina II, a region strongly innervated by nociceptors. These cobalt-positive neurons colocalize with afferents labeled by LD2, and with the most dorsal region of capsaicin-sensitive and IB4- and LA4-positive afferents. In contrast, inner lamina II has a sparser distribution of cobalt-positive neurons. Some lamina I neurons expressing the NK1 receptor, the receptor for substance P, are also cobalt positive. These neurons are likely to be projection neurons in the nociceptive pathway. On the basis of all of these observations, we propose that Ca2+-permeable AMPA receptors are localized to mediate transmission of nociceptive information.  (+info)

Real-time visualization of the cellular redistribution of G protein-coupled receptor kinase 2 and beta-arrestin 2 during homologous desensitization of the substance P receptor. (3/828)

The substance P receptor (SPR) is a G protein-coupled receptor (GPCR) that plays a key role in pain regulation. The SPR desensitizes in the continued presence of agonist, presumably via mechanisms that implicate G protein-coupled receptor kinases (GRKs) and beta-arrestins. The temporal relationship of these proposed biochemical events has never been established for any GPCR other than rhodopsin beyond the resolution provided by biochemical assays. We investigate the real-time activation and desensitization of the human SPR in live HEK293 cells using green fluorescent protein conjugates of protein kinase C, GRK2, and beta-arrestin 2. The translocation of protein kinase C betaII-green fluorescent protein to and from the plasma membrane in response to substance P indicates that the human SPR becomes activated within seconds of agonist exposure, and the response desensitizes within 30 s. This desensitization process coincides with a redistribution of GRK2 from the cytosol to the plasma membrane, followed by a robust redistribution of beta-arrestin 2 and a profound change in cell morphology that occurs after 1 min of SPR stimulation. These data establish a role for GRKs and beta-arrestins in homologous desensitization of the SPR and provide the first visual and temporal resolution of the sequence of events underlying homologous desensitization of a GPCR in living cells.  (+info)

Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury. (4/828)

Upon noxious stimulation, substance P (SP) is released from primary afferent fibers into the spinal cord where it interacts with the SP receptor (SPR). The SPR is located throughout the dorsal horn and undergoes endocytosis after agonist binding, which provides a spatial image of SPR-containing neurons that undergo agonist interaction. Under normal conditions, SPR internalization occurs only in SPR+ cell bodies and dendrites in the superficial dorsal horn after noxious stimulation. After nerve transection and inflammation, SPR immunoreactivity increases, and both noxious as well as nonnoxious stimulation produces SPR internalization in the superficial and deep dorsal horn. We investigated the primary afferent fibers that contribute to enhanced SPR internalization in the spinal cord after nerve transection and inflammation. Internalization evoked by electrical stimulation of the sciatic nerve was examined in untreated animals, at 14 days after sciatic nerve transection or sham surgery and at 3 days after hindpaw inflammation. Electrical stimulation was delivered at intensities to excite Abeta fibers only, Abeta and Adelta fibers or A and C fibers as determined by the compound action potential recorded from the tibial nerve. Electrical stimuli were delivered at a constant rate of 10 Hz for a duration of 5 min. Transection of the sciatic nerve and inflammation produced a 33.7 and 32.5% increase in SPR and immunoreactivity in lamina I, respectively. Under normal conditions, stimulation of Adelta or C fibers evoked internalization that was confined to the superficial dorsal horn. After transection or inflammation, there was a 20-24% increase in the proportion of SPR+ lamina I neurons that exhibited internalization evoked by stimulation of Adelta fibers. The proportion of lamina I SPR+ neurons that exhibited internalization after stimulation of C-fibers was not altered by transection or inflammation because this was nearly maximal under normal conditions. Moreover, electrical stimulation sufficient to excite C fibers evoked SPR internalization in 22% of SPR+ lamina III neurons after nerve transection and in 32-36% of SPR+ neurons in lamina III and IV after inflammation. Stimulation of Abeta fibers alone never evoked internalization in the superficial or deep dorsal horn. These results indicate that activation of small-caliber afferent fibers contributes to the enhanced SPR internalization in the spinal cord after nerve transection and inflammation and suggest that recruitment of neurons that possess the SPR contributes to hyperalgesia.  (+info)

GABAergic neurons that contain neuropeptide Y selectively target cells with the neurokinin 1 receptor in laminae III and IV of the rat spinal cord. (5/828)

Neuropeptide Y (NPY) is contained in a population of GABAergic interneurons in the spinal dorsal horn and, when administered intrathecally, can produce analgesia. We previously identified a strong monosynaptic link between substance P-containing primary afferents and cells in lamina III or IV with the neurokinin 1 (NK1) receptor. Because some of these cells belong to the spinothalamic tract, they are likely to have an important role in pain mechanisms. In this study, we used confocal microscopy to examine the input to lamina III/IV NK1 receptor-immunoreactive neurons from NPY-containing axons. All of the cells studied received a dense innervation from NPY-immunoreactive axons, and electron microscopy revealed that synapses were often present at points of contact. Most NPY-immunoreactive boutons were also GABAergic, which supports the suggestion that they are derived from local neurons. The association between NPY-containing axons and NK1 receptor-immunoreactive neurons was specific, because postsynaptic dorsal column neurons (which were located in laminae III-V but did not possess NK1 receptors) and lamina I neurons with the NK1 receptor received significantly fewer contacts from NPY-immunoreactive axons. In addition, the NK1 receptor-immunoreactive lamina III/IV cells received few contacts from nitric oxide synthase-containing axons (which belong to a different population of GABAergic dorsal horn neurons). The NPY-containing axons appeared to be targeted to the NK1 receptor-immunoreactive neurons themselves rather than to their associated substance P-immunoreactive inputs. The dense innervation of these cells by NPY-containing axons suggests that they may possess receptors for NPY and that activation of these receptors may contribute to NPY-mediated analgesia.  (+info)

Decreased vascular permeability response to substance P in airways of genetically hypertensive rats. (6/828)

1. The inbred genetically hypertensive strain (GH) of the Otago Wistar rat possesses more sensory neurons containing the neuropeptide substance P (SP) than does its genetically related control normotensive strain. 2. As SP contributes to airway inflammation by increasing microvascular permeability, we assessed the extravasation of Evans Blue dye in trachea and main bronchus of anaesthetized GH and control rats, in the presence of endogenous (capsaicin-liberated) or exogenous SP. 3. Following intravenous administration of either capsaicin (75 microg kg(-1)) or SP (3.3 nmol kg(-1)), extravasation of Evans Blue in airways from GH rats was only about 60% of that in airways of control rats. This difference was not gender-specific and responses to capsaicin were abolished by pretreatment with a selective NK1 receptor antagonist SR 140333 (360 nmol kg(-1)). 4. By contrast, the extravasation of dye caused by intravenous 5-hydroxytryptamine (0.5 micromol kg(-1)) was similar in magnitude in both GH and control strains. 5. Falls in systemic arterial blood pressure in response to exogenous SP (0.1-3 nmol kg(-1)) or acetylcholine (0.2-2 nmol kg(-1)) were also very similar between strains, but those in response to capsaicin (75 microg kg(-1)) in the GH rats were about double those in control rats. The hypotensive response to SP was abolished by SR 140333, but that to capsaicin was unaffected. 6. Our results indicate that the increased peripheral innervation density by SP-nerves in GH rats is accompanied by reduced inflammatory responses to SP. This does not involve decreased vasodilator potency of SP and is therefore probably related to altered endothelial responsiveness.  (+info)

Central injections of capsaicin cause antidiuresis mediated through neurokinin-1 receptors in rat hypothalamus and vasopressin release. (7/828)

Intracerebroventricular injections of capsaicin at 100-500 nmol elicited dose-dependent decreases in urine outflow volume in anesthetized, hydrated rats. The capsaicin (500 nmol)-induced antidiuresis was inhibited by pretreatment with CP96345 (30 nmol, a neurokinin-1-receptor antagonist), but not by that with phenoxybenzamine (20 nmol, an alpha-adrenoceptor antagonist), timolol (100 nmol, a beta-adrenoceptor antagonist) or atropine (300 nmol, a muscarinic antagonist) into the hypothalamic supraoptic nucleus (SON). Intravenous injections of d(CH2)5-D-Tyr(Et)VAVP (50 microg/kg, a vasopressin-receptor antagonist) completely blocked the antidiuresis. In intra-SON microdialysis experiments, acetylcholine concentration in the perfusate of the capsaicin-injected rats was not different from that of the vehicle-injected rats. These findings suggested that capsaicin stimulated substance P release in the SON and caused the antidiuresis as a result of the increased release of vasopressin into the circulation from the neurohypophysis mediated through neurokinin-1 receptors in the SON.  (+info)

NK-1 receptor immunoreactivity in distinct morphological types of lamina I neurons of the primate spinal cord. (8/828)

In cat and monkey, lamina I cells can be classified into three basic morphological types (fusiform, pyramidal, and multipolar), and recent intracellular labeling evidence in the cat indicates that fusiform and multipolar lamina I cells are two different types of nociceptive cells, whereas pyramidal cells are innocuous thermoreceptive-specific. Because earlier observations indicated that only nociceptive dorsal horn neurons respond to substance P (SP), we examined which morphological types of lamina I neurons express receptors for SP (NK-1r). We categorized NK-1r-immunoreactive (IR) lamina I neurons in serial horizontal sections from the cervical and lumbar enlargements of four monkeys. Consistent results were obtained by two independent teams of observers. Nearly all NK-1r-IR cells were fusiform (42%) or multipolar (43%), but only 6% were pyramidal (with 9% unclassified). We obtained similar findings in three monkeys in which we used double-labeling immunocytochemistry to identify NK-1r-IR and spinothalamic lamina I neurons retrogradely labeled with cholera toxin subunit b from the thalamus; most NK-1r-IR lamina I spinothalamic neurons were fusiform (48%) or multipolar (33%), and only 10% were pyramidal. In contrast, most (approximately 75%) pyramidal and some (approximately 25%) fusiform and multipolar lamina I spinothalamic neurons did not display NK-1r immunoreactivity. These data indicate that most fusiform and multipolar lamina I neurons in the monkey can express NK-1r, consistent with the idea that both types are nociceptive, whereas only a small proportion of lamina I pyramidal cells express this receptor, consistent with the previous finding that they are non-nociceptive. However, these findings also indicate that not all nociceptive lamina I neurons express receptors for SP.  (+info)

Neurokinin A (NKA) is a neuropeptide belonging to the tachykinin family, which also includes substance P and neurokinin B. It is widely distributed in the central and peripheral nervous systems and plays a role in various physiological functions such as pain transmission, smooth muscle contraction, and immune response regulation. NKA exerts its effects by binding to neurokinin 1 (NK-1) receptors, although it has lower affinity for these receptors compared to substance P. It is involved in several pathological conditions, including inflammation, neurogenic pain, and neurodegenerative disorders.

Neurokinin B is a neuropeptide belonging to the tachykinin family, which also includes substance P and neurokinin A. It is encoded by the TAC3 gene in humans and is widely distributed throughout the central and peripheral nervous systems. Neurokinin B exerts its effects by binding to the neurokinin 3 receptor (NK3R) and plays a role in various physiological processes, including the regulation of feeding behavior, reproduction, and nociception (pain perception). It has also been implicated in several pathological conditions, such as inflammatory diseases, chronic pain, and certain types of cancer.

Neurokinin-2 (NK-2) receptors are a type of G protein-coupled receptor that binds to and is activated by the neuropeptide substance P, which is a member of the tachykinin family. These receptors are widely distributed in the central and peripheral nervous systems and play important roles in various physiological functions, including pain transmission, smooth muscle contraction, and neuroinflammation.

NK-2 receptors are involved in the development of hyperalgesia (an increased sensitivity to pain) and allodynia (pain caused by a stimulus that does not normally provoke pain). They have also been implicated in several pathological conditions, such as inflammatory bowel disease, asthma, and neurodegenerative disorders.

NK-2 receptor antagonists have been developed and investigated for their potential therapeutic use in the treatment of various pain disorders, gastrointestinal diseases, and other medical conditions.

Neurokinin-1 (NK-1) receptors are a type of G protein-coupled receptor that bind to the neuropeptide substance P, which is a member of the tachykinin family. These receptors are widely distributed in the central and peripheral nervous systems and play important roles in various physiological functions, including pain transmission, neuroinflammation, and emesis (vomiting).

NK-1 receptors are activated by substance P, which binds to the receptor's extracellular domain and triggers a signaling cascade that leads to the activation of various intracellular signaling pathways. This activation can ultimately result in the modulation of neuronal excitability, neurotransmitter release, and gene expression.

In addition to their role in normal physiological processes, NK-1 receptors have also been implicated in a number of pathological conditions, including pain, inflammation, and neurodegenerative disorders. As such, NK-1 receptor antagonists have been developed as potential therapeutic agents for the treatment of these conditions.

Tachykinins are a group of neuropeptides that share a common carboxy-terminal sequence and bind to G protein-coupled receptors, called tachykinin receptors. They are widely distributed in the nervous system and play important roles as neurotransmitters or neuromodulators in various physiological functions, such as pain transmission, smooth muscle contraction, and inflammation. The most well-known tachykinins include substance P, neurokinin A, and neuropeptide K. They are involved in many pathological conditions, including chronic pain, neuroinflammation, and neurodegenerative diseases.

Neurokinin-3 (NK-3) receptors are a type of G protein-coupled receptor that binds the neuropeptide neurokinin B, which is a member of the tachykinin family. These receptors are widely distributed in the central and peripheral nervous systems and play important roles in various physiological functions, including the regulation of nociception (pain perception), inflammation, and reproduction.

NK-3 receptors have been identified as key mediators of female reproductive function, particularly in the hypothalamus where they are involved in the control of gonadotropin-releasing hormone (GnRH) secretion. Dysregulation of NK-3 receptor signaling has been implicated in several reproductive disorders, including polycystic ovary syndrome and endometriosis.

In addition to their role in reproduction, NK-3 receptors have also been implicated in various neurological and psychiatric conditions, such as anxiety, depression, and drug addiction. As a result, NK-3 receptor antagonists have emerged as potential therapeutic targets for the treatment of these disorders.

Substance P is an undecapeptide neurotransmitter and neuromodulator, belonging to the tachykinin family of peptides. It is widely distributed in the central and peripheral nervous systems and is primarily found in sensory neurons. Substance P plays a crucial role in pain transmission, inflammation, and various autonomic functions. It exerts its effects by binding to neurokinin 1 (NK-1) receptors, which are expressed on the surface of target cells. Apart from nociception and inflammation, Substance P is also involved in regulating emotional behaviors, smooth muscle contraction, and fluid balance.

Tachykinin receptors are a type of G protein-coupled receptor (GPCR) that bind and respond to tachykinins, which are neuropeptides involved in various physiological functions such as neurotransmission, smooth muscle contraction, vasodilation, and pain perception. There are three main subtypes of tachykinin receptors: NK1, NK2, and NK3.

NK1 receptors primarily bind substance P, a neuropeptide that plays a role in neurotransmission, inflammation, and pain signaling. NK2 receptors mainly bind neurokinin A (NKA) and are involved in smooth muscle contraction, particularly in the respiratory and gastrointestinal tracts. NK3 receptors primarily bind neurokinin B (NKB) and are found in the central nervous system, where they play a role in regulating body temperature, feeding behavior, and sexual function.

Tachykinin receptors have been implicated in various pathological conditions such as chronic pain, inflammation, asthma, and neurodegenerative disorders. As a result, tachykinin receptor antagonists are being developed as potential therapeutic agents for these conditions.

Neurokinin-1 (NK-1) receptor antagonists are a class of drugs that block the action of substance P, a neuropeptide involved in pain transmission and inflammation. These drugs work by binding to NK-1 receptors found on nerve cells, preventing substance P from activating them and transmitting pain signals. NK-1 receptor antagonists have been studied for their potential use in treating various conditions associated with pain and inflammation, such as migraine headaches, depression, and irritable bowel syndrome. Some examples of NK-1 receptor antagonists include aprepitant, fosaprepitant, and rolapitant.

Neurotransmitter receptors are specialized protein molecules found on the surface of neurons and other cells in the body. They play a crucial role in chemical communication within the nervous system by binding to specific neurotransmitters, which are chemicals that transmit signals across the synapse (the tiny gap between two neurons).

When a neurotransmitter binds to its corresponding receptor, it triggers a series of biochemical events that can either excite or inhibit the activity of the target neuron. This interaction helps regulate various physiological processes, including mood, cognition, movement, and sensation.

Neurotransmitter receptors can be classified into two main categories based on their mechanism of action: ionotropic and metabotropic receptors. Ionotropic receptors are ligand-gated ion channels that directly allow ions to flow through the cell membrane upon neurotransmitter binding, leading to rapid changes in neuronal excitability. In contrast, metabotropic receptors are linked to G proteins and second messenger systems, which modulate various intracellular signaling pathways more slowly.

Examples of neurotransmitters include glutamate, GABA (gamma-aminobutyric acid), dopamine, serotonin, acetylcholine, and norepinephrine, among others. Each neurotransmitter has its specific receptor types, which may have distinct functions and distributions within the nervous system. Understanding the roles of these receptors and their interactions with neurotransmitters is essential for developing therapeutic strategies to treat various neurological and psychiatric disorders.

Kisspeptins are a family of peptides that are derived from the preproprotein kisspeptin. The most well-known member of this family is kisspeptin-54, which is also known as metastin. Kisspeptins play important roles in several physiological processes, including the regulation of growth, inflammation, and energy homeostasis. However, they are perhaps best known for their role in the reproductive system.

In the reproductive system, kisspeptins act as key regulators of the hypothalamic-pituitary-gonadal (HPG) axis, which is responsible for controlling reproductive function. Kisspeptins are produced by neurons in the hypothalamus and bind to receptors on other neurons that release gonadotropin-releasing hormone (GnRH). GnRH then stimulates the pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which act on the gonads to promote the production of sex steroids and eggs or sperm.

Dysregulation of the HPG axis, including abnormal kisspeptin signaling, has been implicated in a number of reproductive disorders, such as precocious puberty, delayed puberty, and infertility. As such, there is significant interest in understanding the role of kisspeptins in reproductive function and developing therapies that target this pathway.

Eledoisin is a tachykinin peptide that is found in the venom of certain marine cephalopods, such as the octopus and squid. It is a potent vasodilator and smooth muscle stimulant, and has been studied for its potential therapeutic uses in conditions such as asthma, bronchitis, and cardiovascular disease. However, it has not yet been approved for use in medical treatments.

Isoindoles are not typically considered in the context of medical definitions, as they are organic compounds that do not have direct relevance to medical terminology or human disease. However, isoindole is a heterocyclic compound that contains two nitrogen atoms in its structure and can be found in some naturally occurring substances and synthetic drugs.

Isoindoles are aromatic compounds, which means they have a stable ring structure with delocalized electrons. They can form the core structure of various bioactive molecules, including alkaloids, which are nitrogen-containing compounds that occur naturally in plants and animals and can have various pharmacological activities.

Some isoindole derivatives have been synthesized and studied for their potential medicinal properties, such as anti-inflammatory, antiviral, and anticancer activities. However, these compounds are still in the early stages of research and development and have not yet been approved for medical use.

Therefore, while isoindoles themselves do not have a specific medical definition, they can be relevant to the study of medicinal chemistry and drug discovery.

Physalaemin is defined as a polypeptide toxin that is derived from the skin of certain frog species, specifically in the genus Physalaemus. This peptide contains 24 amino acids and has been found to have various pharmacological effects, including acting as a potent vasodilator, smooth muscle relaxant, and hypotensive agent. It also interacts with opioid receptors in the brain and can produce analgesic (pain-relieving) and hyperalgesic (increased sensitivity to pain) effects. Physalaemin is primarily used in research settings for its pharmacological properties and as a tool to study the structure and function of opioid receptors.

Quinuclidines are a class of organic compounds that contain a unique cage-like structure consisting of a tetrahydrofuran ring fused to a piperidine ring. The name "quinuclidine" is derived from the Latin word "quinque," meaning five, and "clidis," meaning key or bar, which refers to the five-membered ring system that forms the core of these compounds.

Quinuclidines have a variety of biological activities and are used in pharmaceuticals as well as agrochemicals. Some quinuclidine derivatives have been found to exhibit anti-inflammatory, antiviral, and anticancer properties. They can also act as inhibitors of various enzymes and receptors, making them useful tools for studying biological systems and developing new drugs.

It is worth noting that quinuclidines are not typically used in medical diagnosis or treatment, but rather serve as building blocks for the development of new pharmaceutical compounds.

Capsaicin is defined in medical terms as the active component of chili peppers (genus Capsicum) that produces a burning sensation when it comes into contact with mucous membranes or skin. It is a potent irritant and is used topically as a counterirritant in some creams and patches to relieve pain. Capsaicin works by depleting substance P, a neurotransmitter that relays pain signals to the brain, from nerve endings.

Here is the medical definition of capsaicin from the Merriam-Webster's Medical Dictionary:

caпсаісіn : an alkaloid (C18H27NO3) that is the active principle of red peppers and is used in topical preparations as a counterirritant and analgesic.

Pyrrolidonecarboxylic acid, also known as Proline or Prolinic acid, is an organic compound with the formula N-pyrrolidinecarboxylic acid. It is a cyclic amino acid, which means that its side chain is bonded to the rest of the molecule in a ring structure.

Proline is an important constituent of many proteins and plays a crucial role in maintaining the structural integrity of the protein. It is classified as a non-essential amino acid because it can be synthesized by the human body from other amino acids, such as glutamic acid.

Pyrrolidonecarboxylic acid has a variety of uses in medicine and industry, including as a chiral auxiliary in organic synthesis, a building block for pharmaceuticals, and a component in cosmetics and personal care products. It is also used as a buffering agent and a stabilizer in various medical and industrial applications.

Piperidines are not a medical term per se, but they are a class of organic compounds that have important applications in the pharmaceutical industry. Medically relevant piperidines include various drugs such as some antihistamines, antidepressants, and muscle relaxants.

A piperidine is a heterocyclic amine with a six-membered ring containing five carbon atoms and one nitrogen atom. The structure can be described as a cyclic secondary amine. Piperidines are found in some natural alkaloids, such as those derived from the pepper plant (Piper nigrum), which gives piperidines their name.

In a medical context, it is more common to encounter specific drugs that belong to the class of piperidines rather than the term itself.

The arcuate nucleus is a part of the hypothalamus in the brain. It is involved in the regulation of various physiological functions, including appetite, satiety, and reproductive hormones. The arcuate nucleus contains two main types of neurons: those that produce neuropeptide Y and agouti-related protein, which stimulate feeding and reduce energy expenditure; and those that produce pro-opiomelanocortin and cocaine-and-amphetamine-regulated transcript, which suppress appetite and increase energy expenditure. These neurons communicate with other parts of the brain to help maintain energy balance and reproductive function.

Dynorphins are a type of opioid peptide that is naturally produced in the body. They bind to specific receptors in the brain, known as kappa-opioid receptors, and play a role in modulating pain perception, emotional response, and reward processing. Dynorphins are derived from a larger precursor protein called prodynorphin and are found throughout the nervous system, including in the spinal cord, brainstem, and limbic system. They have been implicated in various physiological processes, as well as in the development of certain neurological and psychiatric disorders, such as chronic pain, depression, and substance use disorders.

I must clarify that the term "Guinea Pigs" is not typically used in medical definitions. However, in colloquial or informal language, it may refer to people who are used as the first to try out a new medical treatment or drug. This is known as being a "test subject" or "in a clinical trial."

In the field of scientific research, particularly in studies involving animals, guinea pigs are small rodents that are often used as experimental subjects due to their size, cost-effectiveness, and ease of handling. They are not actually pigs from Guinea, despite their name's origins being unclear. However, they do not exactly fit the description of being used in human medical experiments.

Neuropeptides are small protein-like molecules that are used by neurons to communicate with each other and with other cells in the body. They are produced in the cell body of a neuron, processed from larger precursor proteins, and then transported to the nerve terminal where they are stored in secretory vesicles. When the neuron is stimulated, the vesicles fuse with the cell membrane and release their contents into the extracellular space.

Neuropeptides can act as neurotransmitters or neuromodulators, depending on their target receptors and the duration of their effects. They play important roles in a variety of physiological processes, including pain perception, appetite regulation, stress response, and social behavior. Some neuropeptides also have hormonal functions, such as oxytocin and vasopressin, which are produced in the hypothalamus and released into the bloodstream to regulate reproductive and cardiovascular function, respectively.

There are hundreds of different neuropeptides that have been identified in the nervous system, and many of them have multiple functions and interact with other signaling molecules to modulate neural activity. Dysregulation of neuropeptide systems has been implicated in various neurological and psychiatric disorders, such as chronic pain, addiction, depression, and anxiety.

Calcitonin gene-related peptide (CGRP) is a neurotransmitter and vasodilator peptide that is widely distributed in the nervous system. It is encoded by the calcitonin gene, which also encodes calcitonin and catestatin. CGRP is produced and released by sensory nerves and plays important roles in pain transmission, modulation of inflammation, and regulation of blood flow.

CGRP exists as two forms, α-CGRP and β-CGRP, which differ slightly in their amino acid sequences but have similar biological activities. α-CGRP is found primarily in the central and peripheral nervous systems, while β-CGRP is expressed mainly in the gastrointestinal tract.

CGRP exerts its effects by binding to specific G protein-coupled receptors, which are widely distributed in various tissues, including blood vessels, smooth muscles, and sensory neurons. Activation of CGRP receptors leads to increased intracellular cyclic AMP levels, activation of protein kinase A, and subsequent relaxation of vascular smooth muscle, resulting in vasodilation.

CGRP has been implicated in several clinical conditions, including migraine, cluster headache, and inflammatory pain. Inhibition of CGRP signaling has emerged as a promising therapeutic strategy for the treatment of these disorders.

Smooth muscle, also known as involuntary muscle, is a type of muscle that is controlled by the autonomic nervous system and functions without conscious effort. These muscles are found in the walls of hollow organs such as the stomach, intestines, bladder, and blood vessels, as well as in the eyes, skin, and other areas of the body.

Smooth muscle fibers are shorter and narrower than skeletal muscle fibers and do not have striations or sarcomeres, which give skeletal muscle its striped appearance. Smooth muscle is controlled by the autonomic nervous system through the release of neurotransmitters such as acetylcholine and norepinephrine, which bind to receptors on the smooth muscle cells and cause them to contract or relax.

Smooth muscle plays an important role in many physiological processes, including digestion, circulation, respiration, and elimination. It can also contribute to various medical conditions, such as hypertension, gastrointestinal disorders, and genitourinary dysfunction, when it becomes overactive or underactive.

Bronchoconstriction is a medical term that refers to the narrowing of the airways in the lungs (the bronchi and bronchioles) due to the contraction of the smooth muscles surrounding them. This constriction can cause difficulty breathing, wheezing, coughing, and shortness of breath, which are common symptoms of asthma and other respiratory conditions.

Bronchoconstriction can be triggered by a variety of factors, including allergens, irritants, cold air, exercise, and emotional stress. In some cases, it may also be caused by certain medications, such as beta-blockers or nonsteroidal anti-inflammatory drugs (NSAIDs). Treatment for bronchoconstriction typically involves the use of bronchodilators, which are medications that help to relax the smooth muscles around the airways and widen them, making it easier to breathe.

A peptide fragment is a short chain of amino acids that is derived from a larger peptide or protein through various biological or chemical processes. These fragments can result from the natural breakdown of proteins in the body during regular physiological processes, such as digestion, or they can be produced experimentally in a laboratory setting for research or therapeutic purposes.

Peptide fragments are often used in research to map the structure and function of larger peptides and proteins, as well as to study their interactions with other molecules. In some cases, peptide fragments may also have biological activity of their own and can be developed into drugs or diagnostic tools. For example, certain peptide fragments derived from hormones or neurotransmitters may bind to receptors in the body and mimic or block the effects of the full-length molecule.

The trachea, also known as the windpipe, is a tube-like structure in the respiratory system that connects the larynx (voice box) to the bronchi (the two branches leading to each lung). It is composed of several incomplete rings of cartilage and smooth muscle, which provide support and flexibility. The trachea plays a crucial role in directing incoming air to the lungs during inspiration and outgoing air to the larynx during expiration.

Muscle contraction is the physiological process in which muscle fibers shorten and generate force, leading to movement or stability of a body part. This process involves the sliding filament theory where thick and thin filaments within the sarcomeres (the functional units of muscles) slide past each other, facilitated by the interaction between myosin heads and actin filaments. The energy required for this action is provided by the hydrolysis of adenosine triphosphate (ATP). Muscle contractions can be voluntary or involuntary, and they play a crucial role in various bodily functions such as locomotion, circulation, respiration, and posture maintenance.

Thiorphan is not a medical condition or disease, but rather a synthetic medication. It is a potent inhibitor of membrane-bound metalloendopeptidases, also known as neprilysin enzymes. These enzymes are responsible for breaking down certain peptides in the body, including some hormones and neurotransmitters.

Thiorphan has been used in research to study the role of these enzymes in various physiological processes. It is also being investigated as a potential therapeutic agent for conditions such as hypertension, heart failure, and Alzheimer's disease. However, it is not currently approved for clinical use in humans.

Therefore, there is no medical definition of 'Thiorphan' as a condition or disease.

Benzamides are a class of organic compounds that consist of a benzene ring (a aromatic hydrocarbon) attached to an amide functional group. The amide group can be bound to various substituents, leading to a variety of benzamide derivatives with different biological activities.

In a medical context, some benzamides have been developed as drugs for the treatment of various conditions. For example, danzol (a benzamide derivative) is used as a hormonal therapy for endometriosis and breast cancer. Additionally, other benzamides such as sulpiride and amisulpride are used as antipsychotic medications for the treatment of schizophrenia and related disorders.

It's important to note that while some benzamides have therapeutic uses, others may be toxic or have adverse effects, so they should only be used under the supervision of a medical professional.

Atropine is an anticholinergic drug that blocks the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. It is derived from the belladonna alkaloids, which are found in plants such as deadly nightshade (Atropa belladonna), Jimson weed (Datura stramonium), and Duboisia spp.

In clinical medicine, atropine is used to reduce secretions, increase heart rate, and dilate the pupils. It is often used before surgery to dry up secretions in the mouth, throat, and lungs, and to reduce salivation during the procedure. Atropine is also used to treat certain types of nerve agent and pesticide poisoning, as well as to manage bradycardia (slow heart rate) and hypotension (low blood pressure) caused by beta-blockers or calcium channel blockers.

Atropine can have several side effects, including dry mouth, blurred vision, dizziness, confusion, and difficulty urinating. In high doses, it can cause delirium, hallucinations, and seizures. Atropine should be used with caution in patients with glaucoma, prostatic hypertrophy, or other conditions that may be exacerbated by its anticholinergic effects.

The ileum is the third and final segment of the small intestine, located between the jejunum and the cecum (the beginning of the large intestine). It plays a crucial role in nutrient absorption, particularly for vitamin B12 and bile salts. The ileum is characterized by its thin, lined walls and the presence of Peyer's patches, which are part of the immune system and help surveil for pathogens.

Neurogenic inflammation is a type of inflammatory response that is initiated by the nervous system and involves the release of neurotransmitters and neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP), and nitric oxide. These substances cause vasodilation, increased vascular permeability, and recruitment of immune cells to the site of injury or damage.

Neurogenic inflammation can occur in response to a variety of stimuli, including tissue injury, infection, and chemical or physical irritants. It is thought to play a role in the development and maintenance of various clinical conditions, such as migraine headaches, neuropathic pain, asthma, and allergies.

In contrast to classical inflammation, which is mediated by the immune system, neurogenic inflammation is primarily driven by the nervous system and can occur independently of traditional immune responses. However, the two processes often interact and amplify each other, leading to a more robust and prolonged inflammatory response.

Neurons, also known as nerve cells or neurocytes, are specialized cells that constitute the basic unit of the nervous system. They are responsible for receiving, processing, and transmitting information and signals within the body. Neurons have three main parts: the dendrites, the cell body (soma), and the axon. The dendrites receive signals from other neurons or sensory receptors, while the axon transmits these signals to other neurons, muscles, or glands. The junction between two neurons is called a synapse, where neurotransmitters are released to transmit the signal across the gap (synaptic cleft) to the next neuron. Neurons vary in size, shape, and structure depending on their function and location within the nervous system.

Neprilysin (NEP), also known as membrane metallo-endopeptidase or CD10, is a type II transmembrane glycoprotein that functions as a zinc-dependent metalloprotease. It is widely expressed in various tissues, including the kidney, brain, heart, and vasculature. Neprilysin plays a crucial role in the breakdown and regulation of several endogenous bioactive peptides, such as natriuretic peptides, bradykinin, substance P, and angiotensin II. By degrading these peptides, neprilysin helps maintain cardiovascular homeostasis, modulate inflammation, and regulate neurotransmission. In the context of heart failure, neprilysin inhibitors have been developed to increase natriuretic peptide levels, promoting diuresis and vasodilation, ultimately improving cardiac function.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Afferent neurons, also known as sensory neurons, are a type of nerve cell that conducts impulses or signals from peripheral receptors towards the central nervous system (CNS), which includes the brain and spinal cord. These neurons are responsible for transmitting sensory information such as touch, temperature, pain, sound, and light to the CNS for processing and interpretation. Afferent neurons have specialized receptor endings that detect changes in the environment and convert them into electrical signals, which are then transmitted to the CNS via synapses with other neurons. Once the signals reach the CNS, they are processed and integrated with other information to produce a response or reaction to the stimulus.

Gonadotropin-Releasing Hormone (GnRH), also known as Luteinizing Hormone-Releasing Hormone (LHRH), is a hormonal peptide consisting of 10 amino acids. It is produced and released by the hypothalamus, an area in the brain that links the nervous system to the endocrine system via the pituitary gland.

GnRH plays a crucial role in regulating reproduction and sexual development through its control of two gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These gonadotropins, in turn, stimulate the gonads (ovaries or testes) to produce sex steroids and eggs or sperm.

GnRH acts on the anterior pituitary gland by binding to its specific receptors, leading to the release of FSH and LH. The hypothalamic-pituitary-gonadal axis is under negative feedback control, meaning that when sex steroid levels are high, they inhibit the release of GnRH, which subsequently decreases FSH and LH secretion.

GnRH agonists and antagonists have clinical applications in various medical conditions, such as infertility treatments, precocious puberty, endometriosis, uterine fibroids, prostate cancer, and hormone-responsive breast cancer.

The spinal cord is a major part of the nervous system, extending from the brainstem and continuing down to the lower back. It is a slender, tubular bundle of nerve fibers (axons) and support cells (glial cells) that carries signals between the brain and the rest of the body. The spinal cord primarily serves as a conduit for motor information, which travels from the brain to the muscles, and sensory information, which travels from the body to the brain. It also contains neurons that can independently process and respond to information within the spinal cord without direct input from the brain.

The spinal cord is protected by the bony vertebral column (spine) and is divided into 31 segments: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal. Each segment corresponds to a specific region of the body and gives rise to pairs of spinal nerves that exit through the intervertebral foramina at each level.

The spinal cord is responsible for several vital functions, including:

1. Reflexes: Simple reflex actions, such as the withdrawal reflex when touching a hot surface, are mediated by the spinal cord without involving the brain.
2. Muscle control: The spinal cord carries motor signals from the brain to the muscles, enabling voluntary movement and muscle tone regulation.
3. Sensory perception: The spinal cord transmits sensory information, such as touch, temperature, pain, and vibration, from the body to the brain for processing and awareness.
4. Autonomic functions: The sympathetic and parasympathetic divisions of the autonomic nervous system originate in the thoracolumbar and sacral regions of the spinal cord, respectively, controlling involuntary physiological responses like heart rate, blood pressure, digestion, and respiration.

Damage to the spinal cord can result in various degrees of paralysis or loss of sensation below the level of injury, depending on the severity and location of the damage.

Electric stimulation, also known as electrical nerve stimulation or neuromuscular electrical stimulation, is a therapeutic treatment that uses low-voltage electrical currents to stimulate nerves and muscles. It is often used to help manage pain, promote healing, and improve muscle strength and mobility. The electrical impulses can be delivered through electrodes placed on the skin or directly implanted into the body.

In a medical context, electric stimulation may be used for various purposes such as:

1. Pain management: Electric stimulation can help to block pain signals from reaching the brain and promote the release of endorphins, which are natural painkillers produced by the body.
2. Muscle rehabilitation: Electric stimulation can help to strengthen muscles that have become weak due to injury, illness, or surgery. It can also help to prevent muscle atrophy and improve range of motion.
3. Wound healing: Electric stimulation can promote tissue growth and help to speed up the healing process in wounds, ulcers, and other types of injuries.
4. Urinary incontinence: Electric stimulation can be used to strengthen the muscles that control urination and reduce symptoms of urinary incontinence.
5. Migraine prevention: Electric stimulation can be used as a preventive treatment for migraines by applying electrical impulses to specific nerves in the head and neck.

It is important to note that electric stimulation should only be administered under the guidance of a qualified healthcare professional, as improper use can cause harm or discomfort.

Biphenyl compounds, also known as diphenyls, are a class of organic compounds consisting of two benzene rings linked by a single carbon-carbon bond. The chemical structure of biphenyl compounds can be represented as C6H5-C6H5. These compounds are widely used in the industrial sector, including as intermediates in the synthesis of other chemicals, as solvents, and in the production of plastics and dyes. Some biphenyl compounds also have biological activity and can be found in natural products. For example, some plant-derived compounds that belong to this class have been shown to have anti-inflammatory, antioxidant, and anticancer properties.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

Cyclic peptides are a type of peptides in which the N-terminus and C-terminus of the peptide chain are linked to form a circular structure. This is in contrast to linear peptides, which have a straight peptide backbone with a free N-terminus and C-terminus. The cyclization of peptides can occur through various mechanisms, including the formation of an amide bond between the N-terminal amino group and the C-terminal carboxylic acid group (head-to-tail cyclization), or through the formation of a bond between side chain functional groups.

Cyclic peptides have unique structural and chemical properties that make them valuable in medical and therapeutic applications. For example, they are more resistant to degradation by enzymes compared to linear peptides, which can increase their stability and half-life in the body. Additionally, the cyclic structure allows for greater conformational rigidity, which can enhance their binding affinity and specificity to target molecules.

Cyclic peptides have been explored as potential therapeutics for a variety of diseases, including cancer, infectious diseases, and neurological disorders. They have also been used as tools in basic research to study protein-protein interactions and cell signaling pathways.

A radioligand assay is a type of in vitro binding assay used in molecular biology and pharmacology to measure the affinity and quantity of a ligand (such as a drug or hormone) to its specific receptor. In this technique, a small amount of a radioactively labeled ligand, also known as a radioligand, is introduced to a sample containing the receptor of interest. The radioligand binds competitively with other unlabeled ligands present in the sample for the same binding site on the receptor. After allowing sufficient time for binding, the reaction is stopped, and the amount of bound radioligand is measured using a technique such as scintillation counting. The data obtained from this assay can be used to determine the dissociation constant (Kd) and maximum binding capacity (Bmax) of the receptor-ligand interaction, which are important parameters in understanding the pharmacological properties of drugs and other ligands.

Bethanechol compounds are a type of cholinergic agent used in medical treatment. They are parasympathomimetic drugs, which means they mimic the actions of the neurotransmitter acetylcholine at muscarinic receptors. Specifically, bethanechol compounds stimulate the muscarinic receptors in the smooth muscle of the bladder and gastrointestinal tract, increasing tone and promoting contractions.

Bethanechol is primarily used to treat urinary retention and associated symptoms, such as those that can occur after certain types of surgery or with conditions like spinal cord injury or multiple sclerosis. It works by helping the bladder muscle contract, which can promote urination.

It's important to note that bethanechol should be used with caution, as it can have various side effects, including sweating, increased salivation, flushed skin, and gastrointestinal symptoms like nausea, vomiting, or diarrhea. It may also interact with other medications, so it's crucial to discuss any potential risks with a healthcare provider before starting this treatment.

Posterior horn cells refer to the neurons located in the posterior (or dorsal) horn of the gray matter in the spinal cord. These cells are primarily responsible for receiving and processing sensory information from peripheral nerves, particularly related to touch, pressure, pain, and temperature. The axons of these cells form the ascending tracts that carry this information to the brain for further processing. It's worth noting that damage to posterior horn cells can result in various sensory deficits, such as those seen in certain neurological conditions.

The kidney pelvis, also known as the renal pelvis, is the funnel-shaped part of the upper end of the ureter in the kidney. It receives urine from the minor and major calyces, which are extensions of the renal collecting tubules, and then drains it into the ureter, which carries it to the bladder for storage and eventual elimination from the body. The kidney pelvis is lined with transitional epithelium, which is designed to stretch and accommodate changes in urine volume.

Bethanechol is a parasympathomimetic drug, which means it stimulates the parasympathetic nervous system. This system is responsible for regulating many automatic functions in the body, including digestion and urination. Bethanechol works by causing the smooth muscles of the bladder to contract, which can help to promote urination in people who have difficulty emptying their bladder completely due to certain medical conditions such as surgery, spinal cord injury, or multiple sclerosis.

The medical definition of 'Bethanechol' is:

A parasympathomimetic agent that stimulates the muscarinic receptors of the autonomic nervous system, causing contraction of smooth muscle and increased secretion of exocrine glands. It is used to treat urinary retention and associated symptoms, such as those caused by bladder-neck obstruction due to prostatic hypertrophy or neurogenic bladder dysfunction. Bethanechol may also be used to diagnose urinary tract obstruction and to test the integrity of the bladder's innervation.

"Wistar rats" are a strain of albino rats that are widely used in laboratory research. They were developed at the Wistar Institute in Philadelphia, USA, and were first introduced in 1906. Wistar rats are outbred, which means that they are genetically diverse and do not have a fixed set of genetic characteristics like inbred strains.

Wistar rats are commonly used as animal models in biomedical research because of their size, ease of handling, and relatively low cost. They are used in a wide range of research areas, including toxicology, pharmacology, nutrition, cancer, cardiovascular disease, and behavioral studies. Wistar rats are also used in safety testing of drugs, medical devices, and other products.

Wistar rats are typically larger than many other rat strains, with males weighing between 500-700 grams and females weighing between 250-350 grams. They have a lifespan of approximately 2-3 years. Wistar rats are also known for their docile and friendly nature, making them easy to handle and work with in the laboratory setting.

Protein precursors, also known as proproteins or prohormones, are inactive forms of proteins that undergo post-translational modification to become active. These modifications typically include cleavage of the precursor protein by specific enzymes, resulting in the release of the active protein. This process allows for the regulation and control of protein activity within the body. Protein precursors can be found in various biological processes, including the endocrine system where they serve as inactive hormones that can be converted into their active forms when needed.

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The responses to neurokinin A were also unaffected suggesting that neurokinin A did not mediate its effects via NK‐2 receptors ... 2 receptor ligand, neurokinin A, and on synaptically elicited responses in chloralose‐anaesthetized cats. The effect of ... Electrophysiological Evidence That Neurokinin A Acts Via NK‐1 Receptors in the Cat Dorsal Horn Journal Articles ... Neurokinin A induced a slow, prolonged excitation of 25 of the wide dynamic range neurons. All remaining neurons were ...
Sho Nakamura, Yoshihiro Wakabayashi, Takashi Yamamura, Satoshi Ohkura, and Shuichi Matsuyama "A neurokinin 3 receptor-selective ... The present study aimed to clarify the role of NKB-neurokinin 3 receptor (NK3R) signaling in the pulsatile pattern of GnRH/ ... A neurokinin 3 receptor-selective agonist accelerates pulsatile luteinizing hormone secretion in lactating cattle. ... Sho Nakamura, Yoshihiro Wakabayashi, Takashi Yamamura, Satoshi Ohkura, Shuichi Matsuyama "A neurokinin 3 receptor-selective ...
Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending ... Differential modulation of neurons in the rostral ventromedial medulla by neurokinin-1 receptors. Journal of neurophysiology. ... Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending ... Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending ...
A subset of these receptors plays an important role in pain, including the neurokinin-1 (NK1) receptor, which is activated by a ... Studying NK1 receptors in the lab has the benefit of clinically available drugs that target the receptor, but also comes with ... One reason why drugs targeting the NK1 receptor may not have been effective against pain is that most drugs block receptors at ... highlighting the need for drugs that can reach receptors within cells. G protein-coupled receptors (GPCRs) are a large family ...
IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Receptors,+Neurokinin-1 ... SP binds to all three of the tachykinin receptors, but it binds most strongly to the NK1 receptor. Tachykinin NK1 receptor ... NK1 receptor, as well as the other tachykinin receptors, is made of seven hydrophobic transmembrane (TM) domains with three ... CP-96345 CP-99994 GR-205,171 TAK-637 T-2328 NK1 receptor antagonist Tachykinin receptor Discovery and development of neurokinin ...
Chronic antidepressant drug treatment does not alter neurokinin-1 receptor expression in the rat brain regions ... Chronic antidepressant drug treatment does not alter neurokinin-1 receptor expression in the rat brain regions ...
The expression of neurokinin-1 receptor at striatal and pallidal levels in normal human brain.. Publication Type:. Journal ... Adult, Corpus Striatum, Female, Globus Pallidus, Humans, Immunohistochemistry, Male, Middle Aged, Parvalbumins, Receptors, ... localization methods to human postmortem tissue to compare the distribution of SP and its high affinity receptor neurokinin-1 ( ... Neurokinin-1, Reference Values, Substance P, Tissue Distribution Abstract:. ,p,To further our knowledge of the site of action ...
... or a four-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, dexamethasone, and olanzapine may be ... Which neurokinin 1 receptor antagonists (NK1 RA) are used to prevent chemotherapy-induced nausea and vomiting (CINV)? ... Patients unable to take aprepitant should be offered a 5-HT3 receptor antagonist and dexamethasone; those unable to take ... Minimal emetic risk RT - Offer rescue therapy with a 5-HT3 RA, dexamethasone, or a dopamine receptor antagonist. ...
Check out the study "Challenges in the Development of Intravenous Neurokinin-1 Receptor Antagonists: Results of a Safety and ... Check out the study "First-in-human study of eliapixant (BAY 1817080), a highly selective P2X3 receptor antagonist: ... Check out the study "Single-dose pharmacokinetics, safety, and tolerability of the dual endothelin receptor antagonist ... "Challenges in the Development of Intravenous Neurokinin-1 Receptor Antagonists: Results of a Safety and Pharmacokinetics Dose- ...
The substance P neurokinin 1 receptor (NK1R) regulates motility, secretion, inflammation and pain in the intestine. The ... Localisation and activation of the neurokinin 1 receptor in the enteric nervous system of the mouse distal colon. In: Cell and ... Localisation and activation of the neurokinin 1 receptor in the enteric nervous system of the mouse distal colon. Cell and ... Localisation and activation of the neurokinin 1 receptor in the enteric nervous system of the mouse distal colon. / Pelayo, ...
The effect of single and repeated electroconvulsive shock (ECS) on neurokinin 1 receptor gene expression in the rat brain ... The effect of single and repeated electroconvulsive shock (ECS) on neurokinin 1 receptor gene expression in the rat brain ...
Chronic antidepressant drug treatment does not alter neurokinin-1 receptor expression in the rat brain regions ... Chronic antidepressant drug treatment does not alter neurokinin-1 receptor expression in the rat brain regions ...
... receptor with [3H2]azido-CP-96,345, a photoreactive derivative of a nonpeptide antagonist.在哪里下载?这篇文献在哪里可以阅读?:An azido ... derivative of [3H2](2S, 3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl) methyl)-1-azabicyclo[2.2.2]octon-3-amine (CP-96,345), a ... Nuclear xenobiotic receptor pregnane X receptor locks corepressor silencing mediator for retinoid and thyroid hormone receptors ... Although P2X7 receptors are frequently coexpressed with another subtype of P2X receptor, P2X4, they are believed not to form ...
Receptors, Bombesin * Receptors, Neurokinin-1 * Receptors, Neurotransmitter / drug effects * Receptors, Neurotransmitter / ... Interaction of bombesin and related peptides with receptors on pancreatic acinar cells Ann N Y Acad Sci. 1988:547:138-49. doi: ... R T Jensen 1 , D H Coy, Z A Saeed, P Heinz-Erian, S Mantey, J D Gardner ... 1 Digestive Diseases Branch, National Institute of Diabetes, and Digestive and Kidney Diseases, Bethesda, Maryland 20892. ...
Conversely, mice lacking SP, CGRP or the SP receptor (neurokinin 1 receptor) show reduced pathology in both models of caecal ... including the Frizzled receptors (FZD1, FZD2 and FZD7) in neurons and chondroitin sulfate proteoglycan 4 (CSPG4) in ... into peptidergic sensory neurons that express exogeneous diphtheria toxin receptor (an approach we term toxogenetics) is ... report that TcdB induces neurogenic inflammation by targeting gut-innervating afferent neurons and pericytes through receptors ...
Neurokinin-1 (NK-1) receptor is required in Clostridium difficile- induced enteritis. J Clin Invest. 1998 Apr 15. 101(8):1547- ... Nucleotide-binding oligomerization domain 1 mediates recognition of Clostridium difficile and induces neutrophil recruitment ... in patients aged 1 year and older who are at a high risk for recurrence. ... resulted in a significantly lower rate of recurrence of CDI not associated with the epidemic North American Pulsed Field type 1 ...
... receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of ... Aprepitant is a substance P/neurokinin 1 (NK1) receptor antagonist, an antiemetic agent, chemically described as 5-[[(2R,3S)-2 ... However, the receptor occupancy has not been determined. In addition, the relationship between NK1 receptor occupancy and the ... Animal and human studies show that aprepitant augments the antiemetic activity of the 5-HT3-receptor antagonist ondansetron and ...
A subset of these receptors plays an important role in pain, including the neurokinin-1 (NK1) receptor, which is activated by a ... Studying NK1 receptors in the lab has the benefit of clinically available drugs that target the receptor, but also comes with ... One reason why drugs targeting the NK1 receptor may not have been effective against pain is that most drugs block receptors at ... G protein-coupled receptors (GPCRs) are a large family of proteins that regulate many processes in the body and are the target ...
Pain in knee osteoarthritis is associated with variation in the neurokinin 1/substance P receptor (TACR1) gene. European ... Associations between vitamin D receptor gene polymorphisms and osteoarthritis: an updated meta-analysis. Rheumatology (Oxford, ... Gene-environment interaction between body mass index and transforming growth factor beta 1 (TGFbeta1) gene in knee and hip ... Large-scale meta-analysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip ...
Garnier, Agnès (2016): Neurokinin-1 receptor as a therapeutic target in hepatoblastoma. Dissertation, LMU München: Faculty of ...
... or a four-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, dexamethasone, and olanzapine may be ... Which neurokinin 1 receptor antagonists (NK1 RA) are used to prevent chemotherapy-induced nausea and vomiting (CINV)? ... Patients unable to take aprepitant should be offered a 5-HT3 receptor antagonist and dexamethasone; those unable to take ... Minimal emetic risk RT - Offer rescue therapy with a 5-HT3 RA, dexamethasone, or a dopamine receptor antagonist. ...
As in typical receptor binding, the amount bound will be proportional to the number of free receptors and be related to the on- ... Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Biol Psychiatry. 2004;55: ... E) Release of receptor and ligand from cell. (F) Lysosomal degradation of receptor or ligand. (G) Release of radionuclide from ... Drug action at the 5-HT1A receptor in vivo: autoreceptor and postsynaptic receptor occupancy examined with PET and [carbonyl-11 ...
Inhibition of calcium channels by neurokinin receptor and signal transduction in hamster submandibular ganglion cells ... Tachykinin-induced responses via neurokinin-1 and-3 receptors in hamster submandibular ganglion neurones ... JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM 76(1) 1-8 1999年4月 ... 1 * Modulation of calcium chanels by neuropeptides in ...
Antiemetics: neurotransmitter receptor binding predicts therapeutic actions. Lancet 1982; 1: 658-9. 4. Hamik A, Peroutka SJ. ... and neurokinin-1. Of candidate drugs for PONV, CPZ is the only drug that has activity at the first four of these receptors ... Catecholamines, sympathomimetic drugs and adrenergic receptor antagonists. In: Hardman JG, Limbird LE, editors. Goodman and ... Differential interactions of traditional and novel antiemetics with dopamine D2 and 5-hydroxytryptamine3 receptors. Cancer ...
The neurokinin 1 receptor (NK1R) antagonist serlopitant was the only intervention that we could assess. One study provided low- ... Participants who received serlopitant at doses of 0.25 mg, 5 mg, and 1 mg may be more likely to experience reduced itch ... This study investigated the safety and efficacy of three different doses of oral serlopitant (5 mg, 1 mg, and 0.25 mg, once ... Participants who received serlopitant 1 mg may have a greater rate of relief of patient-reported pruritus intensity as measured ...
Proteinase‐activated receptors (PARs) are receptors that undergo proteolytic activation by proteases. They participate in ... Immunocytochemical localization of the neurokinin 1 receptor in rat dental pulp. Arch Histol Cytol. 2005; 68:259-65. ... a receptor termed the "transient receptor potential, subtype vanilloid 1" or TRPV1, responds to heat, inflammatory mediators ... Vanilloid receptor expression and capsaicin excitation of rat dental primary afferent neurons. J Dent Res. 2001; 80:1518-23. ...
Substance P and its receptor neurokinin 1 expression in asthmatic airways. Journal of Allergy and Clinical Immunology, 2000, ... Summary:Follow the Water Cure and use a 1:1 ratio calcium magnesium multimineral supplement like Solaray Cal-Mag Citrate or Now ... Asthma_1 - 1283, 1233, 4.7. Asthma_2 (all frequencies for 5 min) - 1234, 3672, 7346, 727, 787, 880, 10000, 47, 120. Asthma_v - ... 1)Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma - Effect of clarithromycin. Chest, 2002, Vol 121, Iss 6, pp 1782- ...
Correlation of neurokinin (NK) 1 receptor occupancy in gerbil striatum with behavioral effects of NK1 antagonists. Duffy et al. ... correlation between in vitro receptor interaction and in vivo efficacy. Lindstrom et al.. J.Pharmacol.Exp.Ther., 2007;322:1286 ... The neurokinin-1 receptor is expressed with gastrin-releasing peptide receptor in spinal interneurons and modulates itch. ... Crystal structure of the human NK1 tachykinin receptor. Authors: Yin Et al.. Proc.Natl.Acad.Sci.U.S.A. 2018;115:13264 ...
  • The aim of the present study was to investigate the effects of the non‐peptide NK‐2 receptor antagonist, SR 48968 on the responses of dorsal horn neurons to iontophoretic application of the endogenous NK‐2 receptor ligand, neurokinin A, and on synaptically elicited responses in chloralose‐anaesthetized cats. (mcmaster.ca)
  • In the present studies, we therefore examined changes in responses of RVM neurons to mechanical and heat stimuli after intraplantar injection of capsaicin and determined the role of NK-1 receptors by injecting a NK-1 receptor antagonist into the RVM prior to capsaicin. (umn.edu)
  • Injection of the NK-1 antagonist L-733,060 did not alter evoked responses of ON or OFF cells but attenuated the capsaicin-evoked enhanced responses of ON cells to mechanical and heat stimuli with less of an effect on the enhanced inhibitory responses of OFF cells. (umn.edu)
  • NK1 receptor antagonists block responses to a broader range of emetic stimuli than the established 5-HT3 antagonist treatments. (wikipedia.org)
  • Check out the study "First-in-human study of eliapixant (BAY 1817080), a highly selective P2X3 receptor antagonist: Tolerability, safety and pharmacokinetics. (crs-group.de)
  • An azido derivative of [3H2](2S, 3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl) methyl)-1-azabicyclo[2.2.2]octon-3-amine (CP-96,345), a potent nonpeptide antagonist of the substance P (SP) (neurokinin-1) receptor, was synthesized and shown to have an affinity for the human SP receptor similar to that of the parent compound, CP-96,345. (shengsci.com)
  • EMEND ® is a substance P/neurokinin 1 (NK 1 ) receptor antagonist. (nih.gov)
  • The neurokinin 1 receptor (NK1R) antagonist serlopitant was the only intervention that we could assess. (cochrane.org)
  • CP 99994 dihydrochloride is a high affinity NK 1 antagonist (K i = 0.145 nM in vitro ). (rndsystems.com)
  • Phase 2 Trial of a Neurokinin-1 Receptor Antagonist for the Treatment of Chronic Itch in Epidermolysis Bullosa Patients: A Randomized Clinical Trial. (stanford.edu)
  • Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate. (axonmedchem.com)
  • L-732,138 is a potent and highly selective competitive tachykinin NK 1 receptor antagonist (IC 50 = 2.3 nM). (rndsystems.com)
  • Identification of L-tryptophan derivatives with potent and selective antagonist activity at the NK 1 receptor. (rndsystems.com)
  • Pretreatment with CP-99994, a neurokinin type 1 receptor antagonist, partially abolished the O(3)-induced reactivity to cholinergic agonists and electrical field stimulation. (cdc.gov)
  • Serlopitant is a selective Neurokinin-1 (NK-1) receptor antagonist. (adooq.cn)
  • Vofopitant dihydrochloride (GR 205171A) is a potent, selective and orally available tachykinin neurokinin 1(NK1) receptor antagonist. (adooq.cn)
  • Maropitant is a neurokinin (NK1) receptor antagonist. (adooq.cn)
  • Pavinetant (MLE-4901) is a neurokinin-3 receptor (NK3R) antagonist. (adooq.cn)
  • Befetupitant is a high-affinity, nonpeptide, competitive tachykinin 1 receptor (NK1R) antagonist. (adooq.cn)
  • The percentage of chemotherapy administration involving patients prescribed prophylactic antiemetic drugs, namely, a neurokinin 1 receptor antagonist, serotonin receptor antagonist, and/or dexamethasone, was calculated. (urotoday.com)
  • 28916042 ). N-Acetyltryptophan is an inhibitor of cytochrome c release and an antagonist of the neurokinin 1 receptor (NK-1R). (hmdb.ca)
  • Halothane displayed an initial peak within 2 min which was blocked by atropine but not by the neurokinin 1 (NK1) receptor antagonist CP-99. (lu.se)
  • Cisplatin-based highly emetogenic chemotherapy (HEC) regimens, which are key treatments for some of malignant tumors, were conventionally administered after an antiemetic premedication with dexamethasone plus a 5-hydroxytryptamine 3 receptor antagonist (5-HT 3 RA) such as ondansetron or granisetron. (medscape.com)
  • Aprepitant, a neurokinin-1 (NK-1) receptor antagonist, and palonosetron, a second-generation 5-HT 3 RA, are two recently introduced antiemetic agents expected to improve control of CINV. (medscape.com)
  • However, responses of wide dynamic range neurons to neurokinin A were totally blocked by i.v. administration (0.5 mg/kg) of the NK‐1 receptor antagonists CP‐96,345 ( n = 7) and CP‐99,994 ( n = 5) but not by CP‐96,344 ( n = 4), the inactive enantiomer of CP‐96,345. (mcmaster.ca)
  • We showed previously that injection of NK-1 receptor antagonists into the RVM attenuated mechanical and heat hyperalgesia produced by in-traplantar injection of capsaicin. (umn.edu)
  • NK1 receptor antagonists have also been studied in migraine, emesis and psychiatric disorders. (wikipedia.org)
  • In combination therapy, NK1 receptor antagonists appear to offer better control of delayed emesis and post-operative emesis than drug therapy without NK1 receptor antagonists. (wikipedia.org)
  • It has been reported that centrally-acting NK1 receptors antagonists, such as CP-99994, inhibit emesis induced by apomorphine and loperimidine, which are two compounds that act through central mechanisms. (wikipedia.org)
  • Check out the study "Challenges in the Development of Intravenous Neurokinin-1 Receptor Antagonists: Results of a Safety and Pharmacokinetics Dose-Finding, Phase 1 Study of Intravenous Fosnetupitant" to delve into the key findings and implications. (crs-group.de)
  • Correlation of neurokinin (NK) 1 receptor occupancy in gerbil striatum with behavioral effects of NK1 antagonists. (rndsystems.com)
  • Neurokinin 1 receptor antagonists: correlation between in vitro receptor interaction and in vivo efficacy. (rndsystems.com)
  • Characterization of the interaction of N - acyl -L-tryptophan benzyl ester neurokinin antagonists with the human neurokinin-1 receptor. (rndsystems.com)
  • N-Acyl-L-tryptophan benzyl esters: potent substance P receptor antagonists. (rndsystems.com)
  • Of these, patients who received 24 373 administrations of chemotherapy with a low emetic risk (47.8%) and 633 administrations of chemotherapy with a minimal emetic risk (2.8%) were prescribed serotonin receptor antagonists and dexamethasone. (urotoday.com)
  • Netupitant is in a class of medications called neurokinin (NK1) antagonists. (medlineplus.gov)
  • Palonosetron is in a class of medications called 5-HT 3 receptor antagonists. (medlineplus.gov)
  • There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT 3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). (medscape.com)
  • The neurokinin-1 receptor (NK1R) has recently been described as being pivotal in the development of cancer. (uni-muenchen.de)
  • The tachykinin receptor 1 (TACR1) also known as neurokinin 1 receptor (NK1R) or substance P receptor (SPR) is a G protein coupled receptor found in the central nervous system and peripheral nervous system. (wikipedia.org)
  • To further our knowledge of the site of action of substance P (SP) in the human basal ganglia, we applied single- and double-antigen localization methods to human postmortem tissue to compare the distribution of SP and its high affinity receptor neurokinin-1 (NK1R) at striatal and pallidal levels. (ulaval.ca)
  • SP binds to all three of the tachykinin receptors, but it binds most strongly to the NK1 receptor. (wikipedia.org)
  • Tachykinin NK1 receptor consists of 407 amino acid residues, and it has a molecular weight of 58,000. (wikipedia.org)
  • NK1 receptor, as well as the other tachykinin receptors, is made of seven hydrophobic transmembrane (TM) domains with three extracellular and three intracellular loops, an amino-terminus and a cytoplasmic carboxy-terminus. (wikipedia.org)
  • Crystal structure of the human NK 1 tachykinin receptor. (rndsystems.com)
  • The effect of iontophoretic application of neurokinin A was tested on 51 dorsal horn neurons. (mcmaster.ca)
  • Neurokinin A induced a slow, prolonged excitation of 25 of the wide dynamic range neurons. (mcmaster.ca)
  • SR 48968 (50 pg to 1.0 mg/kg, i.v.) did not affect the on‐going basal activity ( n = 8) or the slow excitation induced by neurokinin A in any of the nine wide dynamic range neurons tested. (mcmaster.ca)
  • To eliminate the possibility that systemically administered SR 48968 may not be reaching central sites, SR 48968 was also applied iontophoretically (70-120 nA) to five neurons and tested against excitatory responses to iontophoretically applied neurokinin A. The on‐going activity of these cells were unaffected by SR 48968. (mcmaster.ca)
  • SR 48968 also had no effect on the excitatory responses of seven neurons to iontophoretic application of the NK‐1 receptor agonist, substance P indicating that substance P actions are not mediated via NK‐2 receptors and that SR 48968 did not react with NK‐1 receptors. (mcmaster.ca)
  • Responses of the neurons to non‐noxious (hair) stimulation ( n = 10), noxious mechanical ( n = 5) and noxious thermal ( n = 8) stimulation of the receptive field were also unaffected by SR 48968, suggesting a lack of participation of NK‐2 receptors in these responses. (mcmaster.ca)
  • These data suggest that neurokinin A, like substance P may be acting via NK‐1, rather than NK‐2 receptors, to produce excitation of wide dynamic range neurons in the dorsal horn of the cat spinal cord. (mcmaster.ca)
  • Neurokinin B (NKB) neurons in the arcuate nucleus of the hypothalamus are considered to play an essential role in generating the pulsatile mode of GnRH/luteinizing hormone (LH) secretion. (bioone.org)
  • Information regarding the distribution of NK 1 R in subtypes of mouse enteric neurons is lacking and is the focus of the present study. (nyu.edu)
  • The remaining NK 1 R- immunoreactive neurons were positive for nitric oxide synthase. (nyu.edu)
  • NK 1 R was expressed by most of the submucosal neurons and was exclusively co-expressed with vasoactive intestinal peptide, with no overlap with choline acetyltransferase. (nyu.edu)
  • Myenteric NK 1 R was mainly expressed by intrinsic primary afferent neurons, with minor expression by descending interneurons and inhibitory motor neurons. (nyu.edu)
  • Submucosal NK 1 R was restricted to non-cholinergic secretomotor neurons. (nyu.edu)
  • Here we report that TcdB induces neurogenic inflammation by targeting gut-innervating afferent neurons and pericytes through receptors, including the Frizzled receptors (FZD1, FZD2 and FZD7) in neurons and chondroitin sulfate proteoglycan 4 (CSPG4) in pericytes. (nature.com)
  • Targeted delivery of the TcdB enzymatic domain, through fusion with a detoxified diphtheria toxin, into peptidergic sensory neurons that express exogeneous diphtheria toxin receptor (an approach we term toxogenetics) is sufficient to induce neurogenic inflammation and recapitulates major colonic histopathology associated with CDI. (nature.com)
  • Immunocytochemistry showed that the percentage of SP-containing neurons in longitudinal trunk and the percentage of neurons innervated by SP-positive nerve fibers in superficial muscular plexus were significantly increased at 1 h after exposure to O(3). (cdc.gov)
  • Phox2a was preferentially associated with smaller ALS neurons, and with those showing relatively weak neurokinin 1 receptor expression. (gla.ac.uk)
  • These neurons appear to be located more superficially and are more sensitive to pruritogenic substances than pain receptors. (medscape.com)
  • The endogenous ligand for this receptor is Substance P, although it has some affinity for other tachykinins. (wikipedia.org)
  • Endogenous ligand for NK 3 receptor. (enzolifesciences.com)
  • The present study aimed to clarify the role of NKB-neurokinin 3 receptor (NK3R) signaling in the pulsatile pattern of GnRH/gonadotropin secretion in postpartum lactating cattle.We examined the effects of the administration of an NK3R-selective agonist, senktide, on gonadotropin secretion in lactating cattle. (bioone.org)
  • Five neurotransmitter receptors are of primary importance in PONV: acetylcholine, dopamine-2, histamine-1, serotonin-3, and neurokinin-1. (ispub.com)
  • [ 5-7 ] Palonosetron has several advantageous features over first-generation 5-HT 3 RA, such as a longer plasma elimination half-life and a higher affinity for the 5-HT 3 receptor. (medscape.com)
  • Participants who received serlopitant at doses of 0.25 mg, 5 mg, and 1 mg may be more likely to experience reduced itch intensity, as reported by the patient, when compared with participants given placebo (low-certainty evidence). (cochrane.org)
  • However, for serlopitant 1 mg and 0.25 mg, the range of possible results indicates there may be little to no difference between groups. (cochrane.org)
  • Studying NK1 receptors in the lab has the benefit of clinically available drugs that target the receptor, but also comes with challenges, as there are large differences between the NK1 receptor in mice and humans. (sciencemission.com)
  • To overcome this, the researchers genetically modified mice to express the human NK1 receptor. (sciencemission.com)
  • In another experiment, the researchers studied mice with a different type of NK1 receptor on the outer membrane of the cell, rather than inside. (sciencemission.com)
  • These mice were more resistant to pain than those with human NK1 receptors inside the cell, illustrating the importance of endosomes in signaling pain and the need for treatments that can penetrate cells. (sciencemission.com)
  • Conversely, mice lacking SP, CGRP or the SP receptor (neurokinin 1 receptor) show reduced pathology in both models of caecal TcdB injection and CDI. (nature.com)
  • Likewise, SP is known to bind to N-methyl-D-aspartate (NMDA) receptors by eliciting excitation with calcium ion influx, which further releases nitric oxide. (wikipedia.org)
  • In the central nervous system (CNS), NO synthesis is primarily triggered by activation of N-methyl-D-aspartate (NMDA) receptors and has a Janus face, with both beneficial and harmful properties. (frontiersin.org)
  • The binding of SP to the NK1 receptor has been associated with the transmission of stress signals and pain, the contraction of smooth muscles and inflammation. (wikipedia.org)
  • The substance P neurokinin 1 receptor (NK 1 R) regulates motility, secretion, inflammation and pain in the intestine. (nyu.edu)
  • Fig. 1: SP-mediated and CGRP-mediated neurogenic inflammation in a TcdB caecum injection model and in a CDI mouse model. (nature.com)
  • In the mouse model that mimics atopic dermatitis in humans, the histamine (H4) receptor mediates both TH-2 inflammation and pruritus. (medscape.com)
  • Patients with a malignant solid tumor who would receive HEC containing 50 mg/m 2 or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). (medscape.com)
  • The responses to neurokinin A were also unaffected suggesting that neurokinin A did not mediate its effects via NK‐2 receptors. (mcmaster.ca)
  • Several FDA-approved drugs that target the NK1 receptor are used to prevent nausea and vomiting associated with chemotherapy or surgery. (sciencemission.com)
  • It works by blocking neurokinin, a natural substance in the brain that causes nausea and vomiting. (medlineplus.gov)
  • Stimulation of opioid mu receptors accentuates pruritus, while stimulation of kappa receptors and blockage of mu receptors suppress pruritus. (medscape.com)
  • Administer EMEND 1 hour prior to chemotherapy on Days 1, 2, and 3. (nih.gov)
  • It is usually taken about 1 hour before the start of chemotherapy with or without food. (medlineplus.gov)
  • These changes allowed the modified netupitant to readily penetrate cells to reach the endosome and block signaling of the NK1 receptor in endosomes with a much more prolonged effect in cells. (sciencemission.com)
  • Summary:Follow the Water Cure and use a 1:1 ratio calcium magnesium multimineral supplement like Solaray Cal-Mag Citrate or Now Full Spectrum Mineral Caps. (electroherbalism.com)
  • Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending facilitation of nociception. (umn.edu)
  • Some of the receptors are cation channels, which can directly depolarize the nociceptor upon activation, while other receptors activate second messenger systems to change neuronal excitability by changing expression of, or modifying the function of, other cation channels. (frontiersin.org)
  • Phase 1/2a Clinical Trial of Gene Corrected Autologous Cell Therapy for Recessive Dystrophic Epidermolysis Bullosa. (stanford.edu)
  • Small Indels in the Androgen Receptor Gene: Phenotype Implications and Mechanisms of Mutagenesis. (medscape.com)
  • The neurokinin-1 receptor is expressed with gastrin-releasing peptide receptor in spinal interneurons and modulates itch. (rndsystems.com)
  • G protein-coupled receptors (GPCRs) are a large family of proteins that regulate many processes in the body and are the target of one third of clinically used drugs. (sciencemission.com)
  • Although we focused on the neurokinin-1 receptor, our findings are likely applicable to many G-protein coupled receptors because many of them show sustained signaling within cells, and therefore require drugs that can enter cells and block the receptors in endosomes," said the senior author. (sciencemission.com)
  • Antiserum generated against a synthetic peptide corresponding to the carboxyl terminus of the human SP receptor immunoprecipitated only the 80-kDa photoaffinity labeled protein, confirming that it is the human SP receptor. (shengsci.com)
  • Interestingly, a second antiserum that was generated against the third extracellular loop of the G protein-coupled receptor no longer immunoprecipitated the receptor when covalently labeled with [3H2]azido-CP-96,345. (shengsci.com)
  • Protein binding site comparisons are frequently used receptor-based techniques in early stages of the dr. (uni-marburg.de)
  • A subset of these receptors plays an important role in pain, including the neurokinin-1 (NK1) receptor, which is activated by a pain-transmitting neuropeptide called substance P. (sciencemission.com)
  • These findings highlight key differences in the neuronal distribution of NK 1 R-IR between the mouse, rat and guinea-pig, with important implications for the functional role of NK 1 R in regulating intestinal motility and secretion. (nyu.edu)
  • [ 1 ] Dramatic relief of renal pruritus after subtotal parathyroidectomy has been described, and findings from 1 study confirmed previous case reports. (medscape.com)
  • The NK-1 receptor is found on human chromosome 2 and is located on the cell's surface as a cytoplasmic receptor. (wikipedia.org)
  • The expression of neurokinin-1 receptor at striatal and pallidal levels in normal human brain. (ulaval.ca)
  • When Chinese hamster ovary cells expressing the human SP receptor were photolabeled with this compound and analyzed with the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, several radioactive bands were observed, including a major band centered at molecular mass 80 kDa, the expected value for the SP receptor expressed in Chinese hamster ovary cells. (shengsci.com)
  • Furthermore, L-ITCcs are innervated by fibers enriched with metabotropic glutamate receptors 7a and/or 8a. (jneurosci.org)
  • These data support the notion that descending facilitation from RVM contributes to hyperalgesia and that NK-1 receptors, presumably located on ON cells, play an important role in initiating descending facilitation of nociceptive transmission. (umn.edu)
  • One reason why drugs targeting the NK1 receptor may not have been effective against pain is that most drugs block receptors at the surface of cells. (sciencemission.com)
  • When NK1 receptors are stimulated, they can generate various second messengers, which can trigger a wide range of effector mechanisms that regulate cellular excitability and function. (wikipedia.org)
  • We demonstrate that L-ITCcs are GABAergic, and strongly express metabotropic glutamate receptor 1α and GABA A receptor α1 subunit, together with moderate levels of parvalbumin. (jneurosci.org)
  • Endothelium-dependent contraction in intrapulmonary arteries: mediation by endothelial NK 1 receptors and TXA 2 . (rndsystems.com)
  • [ 80 ] The study showed that fidaxomicin therapy had a similar efficacy and resulted in a significantly lower rate of recurrence of CDI not associated with the epidemic North American Pulsed Field type 1 strains. (medscape.com)
  • The distribution of NK 1 R-IR within key functional neuronal subclasses was determined by using established neurochemical markers. (nyu.edu)
  • However, the role of TNF-α-TNF receptor 1 (TNFR1) signaling in reparative dentin formation and related inflammatory pathways is not known. (bvsalud.org)
  • Glucagon-like peptide 1 Analogues as Adjunctive Therapy for Patients with Type 1 Diabetes: an Updated Systematic Review and Meta-analysis. (medscape.com)
  • Serum MicroRNA-191-5p Levels in Vascular Complications of Type 1 Diabetes: the EURODIAB Prospective Complications Study. (medscape.com)
  • The distribution of the NK 1 R is a key determinant of the functional effects of substance P in the gut. (nyu.edu)
  • Biological effects resulting from the Cu/Zn-superoxide dismutase-accelerated oxidation of the benzene metabolite 1,4-hydroquinone. (shengsci.com)
  • Insulin signaling through the insulin receptor increases linear growth through effects on bone and the GH-IGF-1 axis. (medscape.com)
  • Cu/Zn-superoxide dismutase (SOD)-accelerated oxidation of the benzene metabolite 1,4-hydroquinone (HQ) results in the enhanced formation of semiquinone anion radicals, electrophilic 1,4-benzoquinone (BQ), and H202. (shengsci.com)
  • The term microdosing, which was introduced through the work of such pioneers as Garner and Lappin ( 1 - 3 ), indicates the potential to assay the plasma pharmacokinetics of a very low administered mass in humans using a highly sensitive means of recording the concentration-time profile. (snmjournals.org)
  • Scientists previously hoped that the NK1 receptor would be a promising target for treating pain-but drugs targeting the receptor failed to control pain in clinical trials in the 1990s and early 2000s. (sciencemission.com)