Interactions between prostaglandin E2 and D-ala2-met-enkephalinamide on adenylate cyclase activity in the guinea-pig superior cervical ganglion.

Crude membrane fractions, obtained from superior cervical ganglia of normal and sympathectomized guinea-pigs, have been used to investigate the role of prostaglandin E2 and D-ala2-met-enkephalinamide in the modulation of ganglionic adenylate cyclase as well as their functional interrelationship. In ganglia from normal animals the enzyme activity was stimulated and inhibited, respectively, by the prostaglandin (10(-4)M) and by the opiate pentapeptide (10(-4)M), while little or no effects were observed in denervated preparations. When the two substances were tested in combination, a supra-additive stimulation of adenylate cyclase activity was obtained both in normal and denervated ganglia. In the latter preparation the opiate increased prostaglandin E2 specific binding, suggesting that the mechanism of supra-additivity could involve interactions at receptors level. Furthermore, the supra-additive stimulation of adenylate cyclase activity by the combination of the two drugs was obtained in a narrow range of concentrations since at low prostaglandin E2 doses (10(-7)-10(-6)M) or at very high doses of the opiate (10(-3)M), only the inhibitory effect of D-ala2-met-enkephalinamide was evidenced.