Distinct functional muscarinic receptors in guinea-pig gallbladder, ileum and atria.
OBJECTIVE
The contractile responses of guinea-pig gallbladder smooth muscle cells have been suggested to be mediated by M3 and M4 muscarinic receptors by different research groups. Therefore, in the present study, several pharmacological properties of cholinergic functions in guinea-pig gallbladder, guinea-pig ileum (mediated via M3 receptors), and guinea-pig and rat atria (mediated via M2 receptors) were compared.


METHODS
The isometric contractions of isolated guinea-pig ileum, guinea-pig gallbladder, guinea-pig and rat atrial strips in in vitro organ bath were recorded on a polygraph and the effects of carbachol, oxotremorine, McN-A-343, and clozapine have been investigated.


RESULTS
Three muscarinic receptor agonists, carbachol, oxotremorine and McN-A-343 showed different order of potencies in their negative inotropic effects and contractile actions in guinea-pig gallbladder suggesting that functional muscarinic receptors in the gallbladder are distinct from those in the atria, and similar to M4-subtypes. Clozapine which was shown to have antagonistic affinity for muscarinic M1, M2, M3 and M5, but partial agonistic affinity for muscarinic M4 receptors, contracted gallbladder concentration-dependently. On the other hand, clozapine antagonised carbachol-induced ileal and gallbladder contractions and negative inotropic effects indicating that it acts like a partial agonist in the gallbladder.


CONCLUSIONS
It was concluded that the contractile muscarinic receptors of guinea-pig gallbladder are distinct from those of atria (M2) and ileum (M3), but seem to be of M4 subtype.
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*