• agonists
  • Shumay E, Gavi S, Wang HY and Malbon CC (2004) Trafficking of beta2‐adrenergic receptors: insulin and beta‐agonists regulate internalisation by distinct cytoskeletal pathways. (els.net)
  • This invention relates to G.alpha.q protein variants and their use in the analysis and discovery of agonists and antagonsists of chemosensory receptors, such as G protein coupled receptors involved in sensing of tastants, olfactants, andpheromones. (patentgenius.com)
  • Here we show that while the carazolol pocket captured in the β 2 AR crystal structure accommodates (-)-isoproterenol and other agonists without steric clashes, a finite movement of the flexible extracellular part of TM-V helix (TM-Ve) obtained by receptor optimization in the presence of docked ligand can further improve the calculated binding affinities for agonist compounds. (pubmedcentralcanada.ca)
  • Tilting of TM-Ve towards the receptor axis provides a more complete description of polar receptor/ligand interactions for full and partial agonists, by enabling optimal engagement of agonists with two experimentally identified anchor sites, formed by Asp113/Asn312 and Ser203/Ser204/Ser207 side chains. (pubmedcentralcanada.ca)
  • Further, receptor models incorporating a flexible TM-V backbone allow reliable prediction of binding affinities for a set of diverse ligands, suggesting potential utility of this approach to design of effective and subtype-specific agonists for adrenergic receptors. (pubmedcentralcanada.ca)
  • Drugs that work to suppress NAN include anticholinergics, benzodiazepines, barbiturates and agonists at the alpha-2 adrenergic receptor in the brain, such as clonidine. (wikipedia.org)
  • citation needed] Physiological processes mediated by the receptor include: CNS: neuronal excitation (most likely responsible for the psychedelic effects associated with 5-HT2A receptor agonists such as LSD, DMT, etc.), behavioural effects, learning, anxiety smooth muscle: contraction (in bronchi and gastrointestinal tract) vasoconstriction / vasodilation platelets: aggregation Activation of the 5-HT2A receptor with 2,5-Dimethoxy-4-iodoamphetamine (DOI) produces potent anti-inflammatory effects in several tissues including cardiovascular and gut. (wikipedia.org)
  • Other 5-HT2A agonists like LSD also have potent anti-inflammatory effects against TNF-alpha-induced inflammation. (wikipedia.org)
  • Role in memory and learning Activation of the 5-HT2A receptor is necessary for the effects of the "classic" psychedelics like LSD, psilocin and mescaline, which act as full or partial agonists at this receptor, and represent the three main classes of 5-HT2A agonists, the ergolines, tryptamines and phenethylamines, respectively. (wikipedia.org)
  • Many drugs and other substances (for example pilocarpine and scopolamine) manipulate these two distinct receptors by acting as selective agonists or antagonists. (wikipedia.org)
  • Research in this area has been limited due to the cardiotoxicity of 5-HT2B agonists, and the lack of clear therapeutic application for 5-HT2B antagonists, but there is still a need for selective ligands for scientific research. (wikipedia.org)
  • 2000
  • While detailed knowledge of ligand-receptor interactions would be instrumental in design of new and improved clinical candidates, the insight into spatial structure of GPCR has been limited to ab initio models ( Goddard and Abrol 2007 ) or models based on rhodopsin crystal structure ( Palczewski and others 2000 ). (pubmedcentralcanada.ca)
  • AT.sub.1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration", Nature, vol. 407, pp. 94-98 (2000). (patentgenius.com)
  • Pharmacology
  • In June of that year, Raymond Ahlquist, Professor of Pharmacology at Medical College of Georgia, published a paper concerning adrenergic nervous transmission. (wikipedia.org)
  • In 1954, he was able to incorporate his findings in a textbook, Drill's Pharmacology in Medicine, and thereby promulgate the role played by α and β receptor sites in the adrenaline/noradrenaline cellular mechanism. (wikipedia.org)
  • GPCRs
  • Although both of the α receptors are GPCRs, there are large differences in their mechanism of action. (wikipedia.org)
  • Specifically, α1 receptors are characterized as Gq GPCRs, signaling through Phospholipase C to increase IP3 and DAG, thus increasing the release of calcium. (wikipedia.org)
  • Meanwhile, α2 receptors are labeled as Gi GPCRs, which signal through Adenylyl Cyclase to decrease cAMP. (wikipedia.org)
  • sub.q protein variants that functionally couple to sensory cell receptors such as taste GPCRs (TRs) and olfactory GPCRs (ORs) in an overly promiscuous manner. (patentgenius.com)
  • Heterotrimeric G proteins, consisting of alpha, beta and gamma subunits, couple ligand-bound seven transmembrane domain receptors (GPCRs or G-protein coupled receptors) to the regulation of effector proteins and production of intracellular secondmessengers such as cAMP, cGMP, and Ca.sup.2+. (patentgenius.com)
  • Many important discoveries in the structure, function, and biology of GPCRs are the result of innovative use of chimeric receptors composed of domains of various GPCRs in an attempt to overcome formidable obstacles. (aspetjournals.org)
  • The central thrust of this review is to ascertain how the chimeric receptor strategy has been applied to studies of GPCRs and what we have learned about the values and limitations of the approach. (aspetjournals.org)
  • The ligand binding domain of GPCRs is not uniform with respect to the role of the N terminus, because for many GPCRs (e.g., adrenergic and serotonergic receptors), the ligand binding occurs somewhere within in the lipid bilayer ( Tota and Strader, 1990 ), although the N terminus and exofacial "loops" must contribute to the forces that organize the binding pocket for the ligand in these receptors. (aspetjournals.org)
  • The cytoplasmic domains of a GPCR include three or four (in the case of palmitoylated GPCRs such as the β 2 -adrenergic receptor and rhodopsin) intracellular loops (iLoops 1-4) and a C-terminal sequence of variable length (70+ residues for β 2 -adrenergic, 20+ residues in Frizzled-1, etc. (aspetjournals.org)
  • This structure, followed by other co-crystals of β 2 AR ( Hanson and others 2008b ) and β 1 AR ( Warne and others 2008 ) with the antagonists (-)-timolol (PDB code 3D4S) and (-)-cyanopindolol (PDB code 2VT4) respectively, represents a leap forward in the understanding of the inactive state of adrenergic GPCRs. (pubmedcentralcanada.ca)
  • This is the main excitatory receptor subtype among the GPCRs for serotonin, although 5-HT2A may also have an inhibitory effect on certain areas such as the visual cortex and the orbitofrontal cortex. (wikipedia.org)
  • noradrenaline
  • The neurotransmitter noradrenaline has higher affinity for the α1 receptor than does adrenaline (which is a hormone). (wikipedia.org)
  • The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline). (wikipedia.org)
  • While the latter conclusion was subsequently shown to be incorrect (it is now known to be noradrenaline), his receptor nomenclature and concept of two different types of dectors mechanisms for a single neurotransmitter, remains. (wikipedia.org)
  • transmembrane
  • there are seven (I-VII) transmembrane‐spanning domains with α‐helical character that create three i loops (i loop 1, 2 and 3), and the C ‐terminus is cytoplasmic. (els.net)
  • antagonism
  • These findings indicate that the PPI-disruptive effect of PCP may be mediated in part by alpha -1 adrenergic receptors and that antagonism of alpha -1 receptors may play a major role in mediating the blockade of PCP-induced deficits in PPI by certain antipsychotics. (aspetjournals.org)
  • These results show that dopamine D4 receptor antagonism in the brain does not result in the same neurochemical consequences (increased dopamine metabolism or hyperprolactinemia) observed with typical neuroleptics. (aspetjournals.org)
  • Clozapine binds to the D4 receptor with the highest affinity compared to other members of the dopamine receptor family that has led to speculations that the atypicality of clozapine may be related to antagonism of dopamine D4 receptors. (aspetjournals.org)
  • In contrast, the EPS and hyperprolactinemia associated with neuroleptics is thought to be a reflection of D2 receptor antagonism in the striatum and pituitary, respectively. (aspetjournals.org)
  • Chronic α1 antagonism may lead to tachyphylaxis acording to the American Heart Association ([1] Drugs That May Cause or Exacerbate Heart Failure, A Scientific Statement From the American Heart Association, Urological Medications). (wikipedia.org)
  • neurons
  • On the other hand, α2 receptors can be found in platelets, cholinergic nerve terminals, some vascular smooth muscle, postsynaptic CNS neurons, and fat cells. (wikipedia.org)
  • Examination of neurons in the posterior cingulate and retrosplenial cortices by electron micrograph revealed apparent lytic breakdown of mitochondria in the large vacuoles which had become apparent 2 hours after administration of an NMDA antagonist. (wikipedia.org)
  • Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-receptor complexes in the cell membranes of certain neurons and other cells. (wikipedia.org)
  • As a consequence of this, nicotinic receptors are often cited as the receptor on the postganglionic neurons at the ganglion. (wikipedia.org)
  • Another role for these receptors is at the junction of the innervated tissues and the postganglionic neurons in the parasympathetic division of the autonomic nervous system. (wikipedia.org)
  • It's now known that muscarinic acetylcholine receptors also appear on the pre-synaptic membrane of somatic neurons in the neuro-muscular junction, where they are involved in the regulation of acetylcholine release. (wikipedia.org)
  • A possible connection has been suggested between mGluRs and neuromodulators, as mGluR1 antagonists block adrenergic receptor activation in neurons. (wikipedia.org)
  • phosphorylation
  • Counterregulation by growth factor receptor tyrosine kinases and homologous desensitization by GRKs share many similarities in receptor phosphorylation, use of accessory proteins and sequestration of the receptors. (els.net)
  • Looft-Wilson RC, Todd SE, Araj CA, Mutchler SM, Goodell CA. Alpha(1)-adrenergic-mediated eNOS phosphorylation in intact arteries. (wm.edu)
  • Yohimbine
  • 1 The pharmacological activity of yohimbine has been well characterized in studies, although these effects may or may not apply to yohimbe, depending on the concentration of yohimbine present. (sigmaaldrich.com)
  • In a study of type 1 and type 2 diabetic rats, pretreatment with yohimbine potentiated glucose-induced insulin release in non-diabetic control rats, and an improvement of oral glucose tolerance in type 2 diabetic rats, but not in type 1 diabetic rats. (sigmaaldrich.com)
  • Yohimbine may act via blockade of postsynaptic alpha-2 adrenoceptors to produce insulinotropic and hypoglycemic effects. (sigmaaldrich.com)
  • Conversely, coadministration of NMDA-antagonists with alpha-2 adrenergic antagonists, like yohimbine could theoretically potentiate NAN. (wikipedia.org)
  • adrenoceptors
  • α1-blockers act on α1-adrenoceptors α2-blockers act on α2-adrenoceptors When the term "alpha blocker" is used without further qualification, it can refer to an α1 blocker, an α2 blocker, a nonselective blocker (both α1 and α2 activity), or an α blocker with some β activity. (wikipedia.org)
  • SR 59230A is a selective antagonist of the beta-3 adrenergic receptor, but was subsequently shown to also act at α1 adrenoceptors at high doses. (wikipedia.org)
  • stimulation
  • However, the subsequent hyperpolarization (IPSP) and slow depolarization (Slow EPSP) that represent the recovery of the postganglionic neuron from stimulation are actually mediated by muscarinic receptors, types M2 and M1 respectively (discussed below). (wikipedia.org)
  • The 5-HT2B receptor stimulation can also lead to pathological proliferation of cardiac valves fibroblasts, which with chronic overstimulation of 5-HT2B can lead to a severe valvulopathy. (wikipedia.org)
  • It has been hypothesized that unopposed α1 blockade could lead to β1-receptor stimulation with increases in renin and aldosterone, leading to edema and weight gain. (wikipedia.org)
  • kinases
  • Counterregulation by growth factor receptor tyrosine kinases and homologous desensitization by GRKs both stimulate the sequestration of β2‐AR. (els.net)
  • mediates
  • Other effects on smooth muscle are contraction in: Ureter Uterus (when pregnant) Urethral sphincter Bronchioles (although minor to the relaxing effect of β2 receptor on bronchioles) Iris dilator muscle Seminal tract, resulting in ejaculation Activation of α1-adrenergic receptors produces anorexia and partially mediates the efficacy of appetite suppressants like phenylpropanolamine and amphetamine in the treatment of obesity. (wikipedia.org)
  • increases
  • Incorporation of G alpha z-Specific Sequence at the Carboxyl Terminus Increases the Promiscuity of Galpha16 toward Gi-coupled Receptors. (patentgenius.com)
  • Activation of the 5-HT2A receptor in hypothalamus causes increases in hormonal levels of oxytocin, prolactin, ACTH, corticosterone, and renin. (wikipedia.org)
  • 1995
  • Cloning of Rat and Mouse P.sub.2Y Purinoceptors", Biochemical and Biophysical Research Communications, vol. 211, No. 1, pp. 211-218 (1995). (patentgenius.com)