Interactions of opiates and prostaglandins E with regard to cyclic AMP in striatal tissue of rats in vitro

Abstract

Summary The effects of prostaglandins E on the concentration of cyclic AMP (cAMP) and a possible antagonism of opiates vs. prostaglandins E were studied in homogenates and in slices of rat striata in vitro. In homogenates, PGE₁ or PGE₂ did not affect the synthesis of cAMP. Morphine slightly lowered the cAMP synthesis, in presence or absence of PGE₁ or PGE₂. In slices, PGE₂ significantly elevated the cAMP concentrations, either in presence or in absence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Morphine, met-enkephalin and levorphanol, but not dextrorphan, antagonized this rise of cAMP. The effect of morphine was antagonized by naloxone. Adenosine or an elevation of K⁺-ions raised the cAMP concentrations, and PGE₂ induced a further increase. In presence of elevated K⁺-ions or adenosine, however, morphine did not antagonize the PGE₂-induced rise of cAMP concentration. It is suggested that under some experimental conditions described in the literature, endogenous activators of cAMP formation, e. g. adenosine, might mask the inhibitory effect of opiates on stimulation of cAMP synthesis induced by prostaglandins E.