Actions of some autacoids and peptides, including relaxin, on costo-uterine muscle from rats.
1. The actions of angiotensin II, bradykinin, oxytocin, arginine vasopressin, relaxin, serotonin and the prostaglandins E2 and F2 alpha were examined on preparations of costo-uterine muscle from stilboestrol-treated rats. 2. All the agonists, except relaxin, when used in concentrations which contract the rat uterus, also produced contractions of costo-uterine muscles. Concentration-response curves were steep and maximal responses to the agonists were comparable. The negative log molar EC50 values were: serotonin, 6.5; angiotensin II, 8.8; bradykinin, 8.4; PGE2, 8.3; PGF2 alpha, 7.1. The EC50 values (units/L) for oxytocin and vasopressin were 4.4 and 2.7 respectively. 3. Indomethacin (2.8 or 5 mumol/L) did not decrease the contractile effects of the peptides or serotonin. The effects of serotonin were reduced, but not reversed, by methysergide (0.94 mumol/L). 4. Porcine relaxin inhibited field stimulation-induced contractions of costo-uterine muscle and uterine horns from immature rats pretreated with oestradiol cypionate and from stilboestrol-treated mature rats. It was much less potent, and its effects were less clearly concentration-related, on costo-uterine muscle. 5. The inhibitory effects of relaxin on the uterus were unaffected by propranolol (1 mumol/L), confirming that on this tissue relaxin acts independently of the release of catecholamines. Progesterone (30 mumol/L) was also without effect on the action of relaxin on the uterus. 6. These results taken together indicate that the costo-uterine muscle of the rat: (i) contracts in response to serotonin and the peptides angiotensin II, arginine vasopressin, bradykinin and oxytocin independently of the release of the contractile prostaglandins F2 alpha and E2; and (ii) in contrast to the uterus, may lack a significant population of receptors for relaxin.(ABSTRACT TRUNCATED AT 250 WORDS)
Fox
D
D
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Handberg
G M
GM
Hartley
M L
ML
Monagle
J
J
Pennefather
J N
JN
D000818:Animals; D012898:Autacoids / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012065:Relaxin / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*
D012898:Autacoids; D010455:Peptides; D012701:Serotonin; D002217:Carbachol; D012065:Relaxin; D011433:Propranolol; D015237:Dinoprost; D015232:Dinoprostone; D007213:Indomethacin; D008784:Methysergide