Morphine diminishes the constancy of spontaneous uterine contractions, antagonizes the positive inotropic effects of prostaglandin E2, but not of prostaglandin F2 alpha and inhibits prostaglandin E and F outputs from the uterus of ovariectomized rats.
The effects of morphine on the constancy of spontaneous contractions (isometric developed tension = IDT and contractile frequency = CF), in uterine strips isolated from ovariectomized rats and the influence of naloxone, were explored. The inotropic responses to added prostaglandins (PGs) E2 and F2 alpha and the influences of morphine and of morphine in the presence of naloxone on PG actions, were also determined. Moreover, the synthesis and outputs of PGs E and F from uteri and the effects of morphine alone and of morphine plus naloxone, were studied. Morphine (10(-6) M) significantly depressed uterine constancy of IDT during the first hours following delivery, but its action on CF did not differ from controls. Naloxone, neither at 10(-8) M nor at 10(-6) M, altered the negative inotropic influence of morphine on IDT. Exogenous PGs E2 and F2 alpha, stimulated uterine inotropism in a concentration-dependent fashion. Morphine altered dose-response curves for exogenous PGE2, evoking a parallel surmountable shift to the right, but did not affect the inotropic action of added PGF2 alpha. This antagonistic effect of the opioid was not altered by preincubation with naloxone. Basal synthesis and outputs of PGs E and F in uteri from ovariectomized rats were significantly depressed by morphine (10(-6) M) but not altered by incubating tissues with morphine in presence of naloxone. Results are discussed in terms of a presumptive dual action of morphine on uterine motility, i.e., antagonizing PGE2 receptors and inhibiting the synthesis of some PGs by the uterus. These influences of morphine do not appear to be subserved by the activation of mu opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Faletti
A
A
Centro de Estudios Farmacológicos y de Principios Naturales (CEFAPRIN), Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET), Buenos Aires, Argentina.
Chaud
M A
MA
Gimeno
M A
MA
Gimeno
A L
AL
D000818:Animals; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D010052:Ovariectomy; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D011458:Prostaglandins E; D011460:Prostaglandins F; D009270:Naloxone; D009020:Morphine; D015237:Dinoprost; D015232:Dinoprostone