Down-regulation of myometrial atrial natriuretic factor receptors by progesterone and pregnancy and up-regulation by oestrogen in rats.
We previously reported that pregnancy and progesterone treatment abolish and ovariectomy reduces the tocolytic activity of atrial natriuretic factor (ANF) on rat uterus. The present study was carried out to determine whether the hormonal state of the animal influences myometrial ANF receptors. A single high-affinity binding site for 125I-labelled ANF(1-28) was detected in myometrial membrane preparations partially purified by discontinuous sucrose gradient centrifugation. The specifically bound ANF could be displaced completely by unlabelled ANF(1-28) (biologically active circulating form of ANF), partially (approximately 50%) by the clearance receptor (ANF-R2) ligand, ANF(4-23), and insignificantly by angiotensin II, vasopressin, carbachol and progesterone. Maximum binding capacities (fmol/mg protein +/- S.E.M.) of myometrial membrane preparations for ANF were as follows: vehicle-treated cyclic rats, 30.2 +/- 5.9 (n = 6); oestrogen-treated virgin rats, 55.8 +/- 7.1 (n = 8); progesterone-treated virgin rats, 21.9 +/- 2.4 (n = 6); 20-day pregnant rats, 18.9 +/- 4.3 (n = 4); ovariectomized rats, undetectable (n = 3); ovariectomized rats treated with oestrogen, 50.2 +/- 4.1 (n = 3); virgin rats treated with progesterone antagonist RU 486, 64.5 +/- 5.2 (n = 3). Relative to cyclic rats, oestrogen and RU 486 caused a significant (P less than 0.05) increase and progesterone and pregnancy caused a significant (P less than 0.05) decrease in ANF myometrial receptors. The hormonal state did not change dissociation constants for ANF binding to myometrial preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
Potvin
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Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Varma
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D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015735:Mifepristone / Q000494:pharmacology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*
D004967:Estrogens; D011956:Receptors, Cell Surface; D015735:Mifepristone; D011374:Progesterone; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor