Pharmacological characterization of muscarinic receptors in the uterus of oestrogen‐primed and pregnant rats

Radioligand binding and contractility studies were undertaken to determine the subtype/s of muscarinic receptors present in uteri of oestrogen‐treated and late pregnant rats. Competition binding studies with uterine membrane preparations and [ 3 H]‐QNB (quinuclidinyl benzilate) provided negative log dissociation constants (p K i ) for each antagonist as follows; oestrogen‐treated – atropine (7.98)himbacine (7.83)>methoctramine (7.52)hexahydrosiladiphenidol (HHSiD; 7.32)5,11‐dihydro‐11‐[[[2‐[2 ‐ [(dipropylamino)methyl] ‐ 1piperidinyl]ethyl]amino] ‐ carbonyl] ‐ 6H‐pyrido‐ [2,3 ‐ b][1,4] ‐ benzodiazepin ‐ 6‐one (AF ‐ DX 384; 7.10)>11 ‐ [[2 ‐ [(diethylamino)methyl]‐1‐piperidinyl]‐ acetyl]5,11‐dihydro‐6H‐pyridol]2,3,‐b][1,4]benzodiazepin‐6‐one (AF‐DX 116, 6.77)>pirenzepine (6.17); late pregnant – atropine (8.05)methoctramine (7.95)himbacine (7.71)HHSiD (7.52)AF‐DX 384 (7.34)>AF‐DX 116 (6.72)>pirenzepine (6.18). The potency of carbachol in causing uterine contraction was similar in preparations from pregnant and non‐pregnant animals (pD 2 =5.57 and 5.46, respectively). Each muscarinic antagonist caused parallel, rightward shifts of carbachol concentration‐response curves. The pA 2 estimates were: oestrogen‐treated – atropine (9.42)>himbacine (8.73)HHSiD (8.68)methoctramine (8.49)AF‐DX 384 (7.91)AF‐DX 116 (7.36)pirenzepine (7.26); late pregnant – atropine (9.48)>himbacine (8.37)HHSiD (8.22)methoctramine (8.01)AF‐DX 116 (7.73)AF‐DX 384 (7.44)pirenzepine (6.92). The relative p K i estimates for antagonists obtained in membrane preparations from oestrogen‐treated rats suggest the presence of muscarinic M 2 subtypes. In functional studies pA 2 values indicated the additional presence of muscarinic M 3 receptor or, possibly an atypical receptor subtype. The similarity between p K i and pA 2 estimates obtained in uteri from oestrogen‐treated and pregnant animals, respectively, indicates that pregnancy does not affect myometrial muscarinic receptors in the rat.British Journal of Pharmacology (1998) 123 , 1639–1644; doi: 10.1038/sj.bjp.0701794