• ligand
  • Efficacy is defined as the ability of a ligand to elicit a response upon binding to a receptor ( Stephenson, 1956 ) and is arguably the most important parameter for optimization in novel agonist drugs. (aspetjournals.org)
  • The ligand also appeared to preferentially promote phosphorylation of Ser412 at the third intracellular loop of the receptor than Ser577 at the C-terminal tail. (le.ac.uk)
  • Receptor theories try to explain signaling events that occur by the interaction of a ligand with its specific receptor. (aspetjournals.org)
  • In recent years, our understanding of how drugs bind and subsequently activate receptors is becoming more complex with many different types of conformations resulting from the binding of various ligands or even the same ligand. (aspetjournals.org)
  • The receptors bind a ligand on the extracellular side and following activation by the drug, causes conformational changes that cause the intracellular loops to bind and activate the heterotrimeric G-protein. (aspetjournals.org)
  • By contrast, nicotinic receptors use a ligand-gated ion channel mechanism for signaling. (wikipedia.org)
  • Binding of the endogenous ligand acetylcholine to the M5 receptor triggers a number of cellular responses such as adenylate cyclase inhibition, phosphoinositide degradation, and potassium channel modulation. (wikipedia.org)
  • Ionotropic receptors are also called Ligand-gated ion channels and they can be excited by neurotransmitters (ligands) like glutamate and aspartate. (wikipedia.org)
  • Ligand-gated ion channels (LGICs) are one type of ionotropic receptor or channel-linked receptor. (wikipedia.org)
  • The direct link between ligand binding and opening or closing of the ion channel, which is characteristic of ligand-gated ion channels, is contrasted with the indirect function of metabotropic receptors, which use second messengers. (wikipedia.org)
  • mAChR
  • This mutant receptor was phosphorylated in response to CNO stimulation in a similar manner as the wild-type M3 mAChR responding to ACh. (le.ac.uk)
  • Similar results were obtained for LY2033298 at the M4 mAChR which suggest that allosteric modulators do not promote a receptor conformation that increases the accessibility of phosphorylation sites to protein kinases. (le.ac.uk)
  • ligands
  • However, orthosteric and allosteric ligands may differentially modulate receptor function and ultimately downstream signaling pathways. (aspetjournals.org)
  • Functional selectivity, which highlights the ability of ligands to differentially activate the signalling pathways linked to G protein-couple receptors (GPCRs) has provided an avenue for developing ligands with greater safety profiles. (le.ac.uk)
  • Although the receptors are conserved in structure, the ligands span a large range of vastly diverse entities from peptides, small molecules, and light. (aspetjournals.org)
  • In this case, binding of the ligands with the receptor causes an ion channel to open, permitting either one or more specific type(s) of ion (e.g. (wikipedia.org)
  • The lack of selective M5 receptor ligands is one of the main reasons that the medical community has such a limited understanding of the M5 receptors effects as the possibility that any and/or all effects of non-selective ligands may be due to interactions with other receptors can not be ruled out. (wikipedia.org)
  • The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides to large proteins. (wikipedia.org)
  • secretion
  • Muscarinic agonists in sufficient dosage can increase secretion of exocrine glands, such as salivary and sweat glands and increase tone of the smooth muscle in the gastrointestinal and urinary tracts. (drugbank.ca)
  • The M1 receptors are common in secretory glands (exocrine glands such as salivary and sweat glands), and their activation results in an increase in secretion from the secretory glands. (drugbank.ca)
  • The M3 receptors are found on smooth muscles and in many glands which help to stimulate secretion in salivary glands, and their activation generally results in smooth muscle contraction and increased glandular secretions. (drugbank.ca)
  • It also inhibits production of amyloidogenic A beta peptide and increases secretion of soluble amyloid precursor protein via stimulation of the M1 receptor as well. (wikipedia.org)
  • These receptors are highly expressed on pancreatic beta cells and are critical regulators of glucose homoestasis by modulating insulin secretion. (wikipedia.org)
  • The muscarinic M3 receptor regulates insulin secretion from the pancreas and are an important target for understanding the mechanisms of type 2 diabetes mellitus. (wikipedia.org)
  • The M3 receptors are also located in many glands, both endocrine and exocrine glands, and help to stimulate secretion in salivary glands and other glands of the body. (wikipedia.org)
  • Pharmacology
  • Partitioning of a drug into the membrane compartment not only potentially depletes drug from the aqueous compartment but also concentrates drug in the local environment around the receptor, which may alter the observed pharmacology of a compound ( Sargent and Schwyzer, 1986 ), particularly if the drug is able to access the target receptor from this compartment. (aspetjournals.org)
  • bronchoconstriction
  • Because the M3 receptor is Gq-coupled and mediates an increase in intracellular calcium, it typically causes constriction of smooth muscle, such as that observed during bronchoconstriction. (wikipedia.org)
  • Vagally-induced bronchoconstriction Mediating olfactory behaviors (e.g. aggression, mating) A structural homolog of M1 receptor is expressed in unicellular eukaryotes, such as Acanthamoeba castellanii. (wikipedia.org)
  • allosteric
  • More recent efforts have focused on the development of allosteric M1AChR modulators that target regions of the receptor distinct from the orthosteric site that are less conserved between family members. (aspetjournals.org)
  • synthesis
  • However, with respect to vasculature, activation of M3 on vascular endothelial cells causes increased synthesis of nitric oxide, which diffuses to adjacent vascular smooth muscle cells and causes their relaxation and vasodilation, thereby explaining the paradoxical effect of parasympathomimetics on vascular tone and bronchiolar tone. (wikipedia.org)
  • ionotropic
  • There are two major types of neurotransmitter receptors: ionotropic and metabotropic. (wikipedia.org)
  • Ionotropic means that ions can pass through the receptor, whereas metabotropic means that a second messenger inside the cell relays the message (i.e. metabotropic receptors do not have channels). (wikipedia.org)
  • parasympathetic
  • In animals CI-1017 improves learning and memory and increases the electrical activity of the hippocampus through activation of the M1 receptor, while minimally producing parasympathetic side effects and only at very high doses. (wikipedia.org)
  • They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers in the parasympathetic nervous system. (wikipedia.org)
  • citation needed] Peripheral autonomic fibers (sympathetic and parasympathetic fibers) are categorized anatomically as either preganglionic or postganglionic fibers, then further generalized as either adrenergic fibers, releasing noradrenaline, or cholinergic fibers, both releasing acetylcholine and expressing acetycholine receptors. (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)
  • There is also some evidence for postsynaptic receptors on sympathetic neurons allowing the parasympathetic nervous system to inhibit sympathetic effects. (wikipedia.org)
  • selectivity
  • Chinese hamster ovary (CHO) cells transfected with plasmid expressing human m1, m3, m4, and m5 were used to determine receptor selectivity of TBPB in a fluorometric imaging plate reader (FLPR) assay. (arvojournals.org)
  • 30-fold selectivity versus M1 and M3, inactive at M2 and M4. (wikipedia.org)
  • Inhibit
  • Experiments in mice have found that M1 and M3 receptor agonists inhibit the formation of amyloid-beta and target GSK-3B. (wikipedia.org)
  • M2 and M4 receptors interact with Gi proteins to inhibit adenylyl cyclase, which results in a decrease of intracellular concentration of cyclic adenosine monophosphate (cAMP). (wikipedia.org)
  • intrinsic efficacy
  • When efficacy was compared with the dissociation rate constant, however, the two were highly correlated, suggesting a relationship between the duration of agonist binding at the receptor and the intrinsic efficacy. (aspetjournals.org)
  • intracellular
  • Relative agonist efficacy was measured at two points after M 3 receptor activation: the stimulation of guanosine 5′- O -(3-[ 35 S]thio)triphosphate binding to Gα subunits, and the subsequent increase in intracellular calcium levels. (aspetjournals.org)
  • Clark recognized that the ability of a drug to produce an intracellular signal depended upon the drug ("fixing") to a receptor and to transduce its action upon the receptor. (aspetjournals.org)
  • Like the M1 muscarinic receptor, M3 receptors are coupled to G proteins of class Gq, which upregulate phospholipase C and, therefore, inositol trisphosphate and intracellular calcium as a signalling pathway. (wikipedia.org)
  • This receptor is bound to intracellular proteins, known as G proteins, which begin the information cascade within the cell. (wikipedia.org)
  • M1, M3 and M5 interact with Gq proteins to stimulate phosphoinositide hydrolysis and the release of intracellular calcium. (wikipedia.org)
  • presynaptic
  • On presynaptic cells, there can be receptor sites specific to the neurotransmitters released by that cell (see Autoreceptor), which provide feedback and mediate excessive neurotransmitter release from it. (wikipedia.org)
  • mediate
  • C-fibers that mediate itch have extremely low conduction velocities (mean, 0.5 m/s), approximately half those of mechano-heat nociceptors, and receptor fields that are approximately three times larger (up to 85 mm in diameter). (asahq.org)
  • Muscarinic receptors mediate many of the effects of acetylcholine in the central and peripheral nervous system. (wikipedia.org)
  • stimulate
  • When compared to methacholine (MCh), a reference agonist, Pilo appeared to preferentially stimulate inositol phosphates production than global receptor phosphorylation. (le.ac.uk)
  • This is due in part because sigma-1 agonists stimulate the anti-apoptoic factor Bcl-2 due to reactive oxygen species dependent transcriptional activation of nuclear factor kB. (wikipedia.org)
  • This gene is a member of the family of human serotonin receptors, which are G protein-coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). (wikipedia.org)