1651. Supra-additive stimulation of adenylate cyclase activity by prostaglandin E2 and D-Ala2-met-enkephalinamide in the guinea-pig superior cervical ganglion: role of Mg2+ions.
- Author
-
Borasio PG, Biondi C, Ferretti ME, Fabbri E, and Pareschi MC
- Subjects
- Animals, Enkephalin, Methionine pharmacology, Guanine Nucleotides pharmacology, Guinea Pigs, Adenylyl Cyclases metabolism, Enkephalin, Methionine analogs & derivatives, Ganglia, Sympathetic metabolism, Magnesium pharmacology, Prostaglandins E pharmacology
- Abstract
Agonists modulation of Mg2(+)-dependent adenylate cyclase activity has been studied in guinea-pig superior cervical ganglion crude membrane preparations. In the absence of receptors ligands, Mg2+ stimulates the enzyme in a concentration-dependent manner. The dose-activation curve shows heterogeneity and two components with "higher" and "lower" apparent affinity states, are extrapolated. In the presence of D-Ala2-met-enkephalinamide only one component is present and the apparent affinity of the ganglionic adenylate cyclase system for the divalent cation as well as Vmax are inhibited. On the contrary, prostaglandin E2 increases affinity and Vmax values of the lower and, to a lesser extent, of the higher Km component. When the two drugs are tested in combination, not only the inhibitory effect of the opiate is overcome, but a large increase of the apparent affinities and Vmax values for both components is obtained, suggesting the involvement of the Mg2(+)-regulated subunits of the adenylate cyclase system in the supra-additive stimulation mechanism of the enzyme.
- Published
- 1989
- Full Text
- View/download PDF