MUSCARINIC RECEPTOR FUNCTION IN THE GUINEA-PIG UTERINE ARTERY IS NOT ALTERED DURING PREGNANCY

The effects of acetylcholine on isolated uterine artery rings of non-p regnant and pregnant guinea-pigs were investigated. Acetylcholine indu ced a concentration- and endothelium-dependent relaxation of both type s of vessels, with similar pD(2) (non-pregnant: pD(2) = 7.66; pregnant : pD(2) = 7.59) and maximal response values. The pK(A) values (non-pre gnant vs. pregnant) of acetylcholine were 6.17 vs. 6.09. The occupancy response relationship was non-linear since the half-maximal response to acetylcholine (non-pregnant vs. pregnant) was obtained with 2.86 vs . 2.91% receptor occupancy. In quiescent preparations, the muscarinic receptor antagonists, atropine, pirenzepine, -[(2-methoxybenzyl)amino] hexyl]-1,8-octane-diamine tetrahydrochloride (methoctramine) and para- fluoro-hexahydro-sila-difenidol (pFHHSiD), produced parallel rightward shifts of the curves for acetylcholine and the slopes of the Schild p lots were not significantly different from unity. The plots constraine d to a slope of unity gave the following -log K-B values (non-pregnant vs. pregnant): atropine (9.68 vs. 9.75), pirenzepine (6.75 vs. 6.53), methoctramine (6.13 vs. 6.23) and pFHHSiD (7.88 vs. 7.96). It is conc luded that, in guinea-pig uterine arteries, acetylcholine induces endo thelium-dependent relaxation and acts as a full agonist, regardless of pregnancy status. We suggest that the relaxation induced by acetylcho line, in either non-pregnant or pregnant guinea-pig uterine artery, is mediated via the M(3) subtype of muscarinic receptors.