A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter.
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Bognar IT, Altes U, Beinhauer C, Kessler I, Fuder H
A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter.
Naunyn Schmiedebergs Arch Pharmacol. 1992 Jun;345(6):611-8.
- PubMed ID
- 1635586 [ View in PubMed]
- Abstract
In order to analyse the subtype of muscarinic receptors involved in the methacholine-induced contraction of the rabbit iris sphincter we have determined equilibrium dissociation constants (KB) of various antagonists in the sphincter muscle. The values were compared with those observed at M1 (rabbit vas deferens), M2 (heteroreceptors in rat iris) and M3 receptors (guinea-pig ileum), or at the muscarinic receptors in the guinea-pig uterus. The methacholine-induced contraction of the uterus from immature guinea-pigs was competitively antagonized by pirenzepine (6.64, -log KB), 4-DAMP (8.39), hexahydrodifenidol (HHD; 7.00 for the (R)- and 5.40 for the (S)-enantiomer), p-fluoro-hexahydrosiladifenidol (p-F-HHSiD; 6.25) and valethamate bromide (8.04). The affinity of the antagonists is consistent with the presence of an M2 receptor. The -log KB values of the antagonists in the rabbit iris sphincter (6.43, p-F-HHSiD; 6.22, AQ-RA 741; 7.23 and 5.34, (R)- and (S)-trihexyphenidyl) were lower than, or within the lowest range of, estimates in the other experimental models, irrespective of the subtype selectivity of the antagonist. This excludes the presence of an M1, M2, M3 or M4 receptor in this smooth muscle. The affinity of UH-AH 37 in the iris was intermediate between that for M1 or M3, and M2 receptors. The low affinity of AQ-RA 741 and the low enantiomeric ratio of trihexyphenidyl (THP) in the iris (77.6) would be compatible with a presumed M5 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Trihexyphenidyl Muscarinic acetylcholine receptor M2 Protein Humans UnknownAntagonistDetails Trihexyphenidyl Muscarinic acetylcholine receptor M3 Protein Humans UnknownAntagonistDetails Trihexyphenidyl Muscarinic acetylcholine receptor M4 Protein Humans UnknownAntagonistDetails Trihexyphenidyl Muscarinic acetylcholine receptor M5 Protein Humans UnknownAntagonistDetails