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Start Over Subject muscarinic receptors

1. Binding of phenylcyclohexylglycoloyl ester of hydroxyethyldimethylhydrazonium (compound VUFB-3113) to muscarinic receptors in rat heart, salivary gland and cerebral cortex

Creator:
Mysliveček jr., J. and Tuček, S.
Type:
article, model:article, and TEXT
Subject:
muscarinic receptors, heart, salivary gland, phenylcyclohexylglycoloyloxyethyldimethylhydrazonium, and brain cortex
Language:
English
Description:
Phenylcyclohexylglycoloylester of hydroxyethyldimethylhydrazonium (compound VGFB-3113) has been shown earlier to have a strong antimuscarinic effect on smooth muscle. Its affinity to muscarinic binding sites in homogenates of rat heart ventricles (M2 subtype), submandibular salivary gland (M3 subtype) and brain cortex (predominantly Ml subtype) has now been investigated in radioligand displacement experiments using (3H)quinuclidinyl benzilate ((3H)QNB) as a relatively non-specific muscarinic ligand. VGFB-3113 inhibited the binding of (3H)QNB with pKj values of 8.17, 8.73, and 8.52 in the heart, salivary gland, and brain cortex, respectively. It is concluded that the compound has a high affinity for muscarinic binding sites without strong preference for any of the Ml-M3 subtypes.
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public

2. Outline of therapeutic interventions with muscarinic receptor-mediated transmission

Creator:
Jaroslav Jakubík, Šantrůčková, E., Randáková, A., Hana Janíčková, Petr Zimčík, Rudajev, V., Michal, P., Esam E. El-Fakahany, and Vladimír Doležal
Format:
print
Type:
article, články, model:article, and TEXT
Subject:
Fyziologie člověka a srovnávací fyziologie, fyziologie, physiology, muscarinic receptors, g-proteins, allosteric modulators, ectopic agonists, selectivity, 14, and 612
Language:
English
Description:
Muscarinc receptor-mediated signaling takes part in many physiological functions ranging from complex higher nervous activity to vegetative responses. Specificity of action of the natural muscarinic agon ist acetylcholine is effected by action on five muscarinic receptor subtypes with particular tissue and cellular localization, and coupling preference with different G-proteins and their signalin g pathways. In addition to physiological roles it is also implicated in pathologic events like promotion of carcinoma cells growth, early pathogenesis of neurodegenerative diseases in th e central nervous system like Alzheimer's disease and Parkinson's disease, schizophrenia, intoxications resulting in drug addiction, or overactive bladder in the periphery. All of these disturbances demonstrate involvement of specific muscarinic receptor subtypes and point to the importance to develop selective pharmacotherapeutic interventions. Because of the high homology of the orthosteric binding site of muscarinic receptor subtypes there is virtually no subtype selective agonist that binds to this site. Activation of specific receptor subtypes may be achieved by developing allosteric modulators of acetylcholine binding, since ectopic binding domains on the receptor are less conserved compared to the orthosteric site. Potentiation of the effects of acetylcholine by allosteric modulators would be beneficial in cases where acetylcholine release is reduced due to pathological conditions. When presynaptic function is severly compromised, the utilization of ectopic agonists can be a thinkable solution., J. Jakubík ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Rights:
http://creativecommons.org/licenses/by-nc-sa/4.0/ and policy:public