Effect of estrogen on muscarinic acetylcholine receptor expression in rat myometrium.
We report the effect of acute estrogen treatment in the expression of muscarinic acetylcholine receptors (mAChRs) in myometrium. Strips were obtained from rats in estrus (control) and treated with estrogen, 24h before the experiments. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed and m2, m3 and m5 mAChR mRNA subtypes were detected in myometrium from both groups. [(3)H]Quinuclidinyl benzilate [(3)HQNB] binding studies indicated that estrogen treatment did not change the affinity and density of mAChRs in myometrial membranes. Displacement curves of [(3)HQNB] with different mAChRs antagonists indicated a one-site fit for all antagonists tested. Comparison of pK(i) values indicated a significant correlation to M(2)-mAChR subtype. Functional studies, however, showed that estrogen treatment increased myometrium sensitivity to carbachol and the calculated apparent affinity values were significantly correlated to M(3)-mAChR. Furthermore, the pharmacological profile of the two populations of mAChR was not affected by estrogen. In conclusion, these results provide evidence for the presence of M(2)- and M(3)-mAChR, at the mRNA and protein level, in the rat myometrium and indicate that estrogen induces an increase in myometrial responsiveness to mAChR agonists.
Abdalla
Fernando M F
FM
Laboratory of Pharmacology, Instituto Butantan, São Paulo, SP, Brazil.
Maróstica
Elisabeth
E
Picarelli
Zuleika P
ZP
Abreu
Lygia C
LC
Avellar
Maria Christina W
MC
Porto
Catarina S
CS
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009215:Myometrium / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000187:drug effects / Q000235:genetics; D043587:Receptor, Muscarinic M3 / Q000187:drug effects / Q000235:genetics; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000235:genetics
D004967:Estrogens; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D012333:RNA, Messenger; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D002217:Carbachol