Novel pharmacological profile of muscarinic receptors mediating contraction of the guinea-pig uterus

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 342; no. 3; p. 284
• Main Authors: Dörje, F, Friebe, T, Tacke, R, Mutschler, E, Lambrecht, G
• Format: Journal Article
• Language: English
• Published: Germany 01.09.1990
• Subjects: Animals; Female; Guinea Pigs; Ileum - drug effects; In Vitro Techniques; Male; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Myocardial Contraction - drug effects; Parasympatholytics - pharmacology; Rabbits; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; Uterine Contraction - drug effects; Vas Deferens - drug effects
• ISSN: 0028-1298
• DOI: 10.1007/BF00169439

The present study was designed to further characterize the muscarinic receptors mediating contraction of the guinea-pig uterus. The affinities of various selective muscarinic antagonists were determined and compared with those obtained at M1 (rabbit vas deferens), M2 (guinea-pig atria) and M3 receptors (guinea-pig ileum). The contractile responses of uterine smooth muscle from immature guinea-pigs to carbachol (pD2 = 5.73) were competitively antagonized by pirenzepine (pA2 = 7.04), AF-DX 116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11- dihydro-6H-pyrido[2,3-b][1.4]benzo,diazepin-6-one) (pA2 = 6.96), himbacine (pA2 = 7.92), methoctramine (pA2 = 7.52), 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide) (pA2 = 8.87) and sila-hexocyclium (pA2 = 8.81). A comparison of affinity values indicates that the muscarinic receptors present in guinea-pig uterus display a novel pharmacological profile which is not consistent with the presence of either an M1, M2 or M3 receptor. The affinities determined for the different antagonists rather showed a close similarity to those obtained at muscarinic receptors present in rat striatum and NG108-15 cells which are considered pharmacological equivalents (M4 receptors) of the m4 gene product. We thus hypothesize that the guinea-pig isolated uterus preparation may serve as a simple functional assay system to study the pharmacology of M4 receptors.