Characterization of muscarinic receptors in guinea-pig uterus

• Published in: European journal of pharmacology Vol. 250; no. 2; pp. 223 - 230
• Main Authors: Doods, Henri N., Willim, Klaus D., Boddeke, Hendrikus W.G.M., Entzeroth, Michael
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 07.12.1993; Elsevier
• Subjects: Animals; Biological and medical sciences; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; CHO Cells; Cricetinae; Female; Fundamental and applied biological sciences. Psychology; Guinea Pigs; In Vitro Techniques; m4 binding site; Male; Mammalian female genital system; Morphology. Physiology; Muscarinic M 2 receptor; Muscarinic receptor; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Myocardium - metabolism; Parasympatholytics - pharmacokinetics; Parasympathomimetics - pharmacokinetics; Radioligand Assay; Rats; Rats, Wistar; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - metabolism; Smooth muscle; Submandibular Gland - drug effects; Submandibular Gland - metabolism; Uterine Contraction - drug effects; uterus; Uterus - drug effects; Uterus - metabolism; Vertebrates: reproduction; Smooth muscle; Muscarinic receptor; uterus; m4 binding site; Muscarinic M 2 receptor; Vertebrata; Mammalia; Guinea pig; Uterus; Female genital system; Rodentia
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(93)90385-U

To characterize the muscarinic receptor present in guinea-pig uterus smooth muscle the affinities of a series of 27 muscarinic receptor antagonists for M 1 (rat cortex), M 2 (rat heart), M 3 (rat submandibular gland), m4 (transfected in CHO cells) and muscarinic binding sites in guinea-pig uterus smooth muscle were determined in radioligand binding studies. In addition, functional experiments were performed to assess p K B values of the antagonist for muscarinic receptors in guinea-pig atrium and uterus. The results obtained are consistent with the presence of M 2 receptors in the uterus through which the functional contractile response is mediated. Correlation coefficients of 0.98, 0.91 and 0.91 were calculated for the following linear regressions: p K i uterus vs. p K i M 2, p K B uterus vs. p K i M 2and p K B uterus vs. p K B atrium. This study also revealed that the compounds dicyclomine, DAU 5884, DAU 6202 as well as AQ-RA 721 could distinguish m4 from M 2 sites and are therefore important tools to characterize muscarinic receptor subtypes. In addition, DAU 5884 and DAU 6202 have been identified as highly potent M 1 selective antagonists.