On the relation between release of prostaglandins and contractility of rabbit splenic capsular strips

Abstract

Rabbit splenic capsular strips release prostaglandins E and F when contracted by noradrenaline or methoxamine. Contractions and prostaglandin release are dose-dependent. Cocaine increases significantly the effect of noradrenaline, but not that of methoxamine, on contraction of the strips and release of prostaglandin E. Release of prostaglandin F was increased by the addition of cocaine not only when noradrenaline was used as an agonist but also at two of three dose levels of methoxamine. When indometacin is added to the bath fluid, it inhibits prostaglandin release and at the same time potentiates the contractile effects of noradrenaline and methoxamine on the rabbit splenic capsular strips. The prostaglandin-synthetase blocker 5,8,11,14-eicosatetraynoic acid also potentiates the contractions induced by noradrenaline and methoxamine. Both the effects on prostaglandin synthesis and on contraction exerted by indometacin can be reversed, when indometacin is washed out. Exogenous prostaglandins E1, E2 and F2alpha in concentrations up to 150 ng/ml do not influence contractions of the strips induced by either noradrenaline or methoxamine. At higher concentrations prostaglandin E1 decreases, but prostaglandins E2 and F2alpha increase the contractions induced by both agonists. The potentiation of the effects of noradrenaline and methoxamine on rabbit splenic strips by indometacin and 5,8,11,14-eicosatetraynoic acid cannot be explained by inhibition of uptake1 or uptake2, release of endogenous noradrenaline or inhibition of metabolism of the agonists. It is suggested that the potentiation is caused by inhibition of synthesis of endogenous prostaglandins, although an undefined sensitizing effect of indometacin and 5,8,11,14-eicosatetraynoic acid cannot be completely exclused.