title: Subtypes of muscarinic receptors in rat duodenum: a comparison with rabbit vas deferens, rat atria, guinea-pig ileum and gallbladder by using imperialine.
abstract: The specific binding of [3H]QNB to rat duodenum smooth muscle membranes was a saturable process and Scatchard transformation of the saturation curves indicated a linear plot (nH = 1.017+/-0.071). The K(D) and Bmax values were 0.168+/-0.025 nM and 46.7+/-8.6 fmol/mg protein, respectively. Analyses of competition curves using pirenzepine and guanylpirenzepine indicated more than one class of binding site. A minor population of muscarinic binding sites showed high affinity (M1) for both pirenzepine (19.3+/-1.2%; pKi = 8.29+/-0.36) and guanylpirenzepine (29.4+/-2.0%; pKi = 7.28+/-0.11). The antagonistic affinity values of pirenzepine and guanylpirenzepine for the remaining low affinity binding sites, and that of methoctramine indicated the presence of both M2 and M3 subtypes. McN-A-343 produced relaxations in rat duodenum and inhibited twitch contractions of rabbit vas deferens induced by electrical stimulation in a concentration dependent manner. Carbachol (Cch) exerted concentration-dependent negative inotropic effect in rat atria and contractile effects in guinea-pig gallbladder and ileum longitudinal muscle-myenteric plexus preparation. Imperaline displaced the concentration-response curves to McN-A-343 and Cch to the right in parallel, without affecting the maximum responses in all tissues studied. The rank order of the pA2 values was rabbit vas deferens > rat atria > guinea-pig gallbladder = guinea-pig ileum > rat duodenum. The presynaptic muscarinic receptors at the rat duodenum and rabbit vas deferens were concluded to be of M1 and M4 subtypes, respectively.
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002595:Cevanes / Q000378:metabolism; D003959:Diamines / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D018727:Muscarinic Antagonists / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*