caa a22 4500 46907910X CHVBK 20180323132944.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF00164573 doi (NATIONALLICENCE)springer-10.1007/BF00164573 A muscarinic receptor different from the M1, M2, M3 and M4 subtypes mediates the contraction of the rabbit iris sphincter [Elektronische Daten] [I. Bognar, U. Altes, C. Beinhauer, I. Kessler, H. Fuder] Summary: 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 (pF-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 AQRA 741 and the low enantiomeric ratio of trihexyphenidyl (THP) in the iris (77.6) would be compatible with a presumed M5 receptor. Valethamate bromide and clozapine did not differentiate between M1, M2 and M3 receptors in the present functional studies; the pA2 values at the M1-M3 sites (8.46-8.57 and 7.26-7.58, respectively) were about 10 and 100 times higher, respectively, than the estimates in the iris sphincter. In absolute terms, however, our −log KB values of the THP-enantiomers, UH-AH 37 and clozapine in the iris sphincter were 0.8-2 log units lower than previous data on cloned m5 receptors suggesting receptor properties different from the presumed M5 receptor. In conclusion, the muscarinic receptors in the rabbit iris sphincter may represent a novel type differing from M1-M4 receptors. Springer-Verlag, 1992 Muscarinic receptor subtypes nationallicence Rabbit iris sphincter muscle nationallicence Guinea-pig uterus nationallicence Rat iris nationallicence Preand postjunctional dissociation constants nationallicence Bognar I. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut Altes U. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut Beinhauer C. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut Kessler I. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut Fuder H. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 611-618 0028-1298 345:6<611 1992 345 210 https://doi.org/10.1007/BF00164573 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00164573 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bognar I. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut NATIONALLICENCE 700 1- Altes U. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut NATIONALLICENCE 700 1- Beinhauer C. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut NATIONALLICENCE 700 1- Kessler I. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut NATIONALLICENCE 700 1- Fuder H. Pharmakologisches Institut der Universität, Obere Zahlbacher Strasse 67, W-6500, Mainz, Federal Republic of Germany aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/6(1992-06-01), 611-618 0028-1298 345:6<611 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer