CHARACTERIZATION OF MUSCARINIC RECEPTORS IN GUINEA-PIG UTERUS

To characterize the muscarinic receptor present in guinea-pig uterus s mooth muscle the affinities of a series of 27 muscarinic receptor anta gonists for M1 (rat cortex), M2 (rat heart), M3 (rat submandibular gla nd), m4 (transfected in CHO cells) and muscarinic binding sites in gui nea-pig uterus smooth muscle were determined in radioligand binding st udies. In addition, functional experiments were performed to assess pK (B) values of the antagonist for muscarinic receptors in guinea-pig at rium and uterus. The results obtained are consistent with the presence Of M2 receptors in the uterus through which the functional contractil e response is mediated. Correlation coefficients of 0.98, 0.91 and 0.9 1 were calculated for the following linear regressions: pK(i) uterus v s. pK(i) M2, pK(B) uterus vs. pK(i) M2 and pK(B) uterus vs. pK(B) atri um. This study also revealed that the compounds dicyclomine, DAU 5884, DAU 6202 as well as AQ-RA 721 could distinguish m4 from M2 sites and are therefore important tools to characterize muscarinic receptor subt ypes. In addition, DAU 5884 and DAU 6202 have been identified as highl y potent M1 selective antagonists.