Supra-additive activation of guinea-pig superior cervical ganglion adenylate cyclase by PGE2 and D-Ala2-Met-enkephalinamide: role of GTP.

The effects of guanine nucleotides were tested on basal and agonist-modulated adenylate cyclase in guinea-pig superior cervical ganglion crude membrane preparations. GTP gamma S and Gpp(NH)p dose-dependently stimulate, while GDP beta S inhibits, both the basal and the prostaglandin E2-stimulated enzyme activity. Low GTP doses, up to 10(-5) M, stimulate, while higher doses inhibit, the ganglionic adenylate cyclase. The GTP-induced diphasic pattern is maintained also in the presence of prostaglandin E2, D-Ala2-Met-enkephalinamide, or a combination of the two drugs. However, the opioid inhibits the enzyme activity, but only at high GTP doses, while the prostaglandin stimulates the enzyme at all GTP concentrations. The effect is potentiated by a combination of prostaglandin and enkephalin. The enhancing effect of the prostaglandin and of the combination with enkephalin is maximally expressed at high, almost physiological, GTP doses.