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-pregnant and pregnant guinea-pigs were investigated. Acetylcholine induced a concentration- and endothelium-dependent relaxation of both types of vessels, with similar pD2 (non-pregnant: pD2 = 7.66; pregnant: pD2 = 7.59) and maximal response values. The pKA values (non-pregnant 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, N,N'-bis[6-[(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 plots were not significantly different from unity. The plots constrained to a slope of unity gave the following -log KB 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 concluded that, in guinea-pig uterine arteries, acetylcholine induces endothelium-dependent relaxation and acts as a full agonist, regardless of pregnancy status. We suggest that the relaxation induced by acetylcholine, in either non-pregnant or pregnant guinea-pig uterine artery, is mediated via the M3 subtype of muscarinic receptors.
Jovanović
A
A
Department of Pharmacology, Medical Faculty, Belgrade, Yugoslavia.
Grbović
L
L
Drekić
D
D
Novaković
S
S
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D014599:Uterus / Q000098:blood supply*
D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D000109:Acetylcholine