Pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide-stimulated cyclic AMP synthesis in rat cerebral cortical slices - Interaction with noradrenaline, adrenaline, and forskolin

Pituitary adenylate cyclase-activating polypeptide (PACAP; 0.001-1 muM) and vasoactive intestinal peptide (VIP; 0.01-1 muM) produced a concentration-dependent stimulation of cyclic AMP (cAMP) formation in rat cerebral cortical slices prelabeled with [H-3]adenine. The effects of PACAP(38) and PACAP(27) were similar, and more efficacious (at 0.1 and 1 muM) than those of VIP. Adrenaline and noradrenaline (each at 100 M) also stimulated cAMP formation, with the latter compound being more effective. Combination of PACAP(38), PACAP(27) (each at 0.1 muM) and VIP (1 muM) with adrenaline or noradrenaline resulted in most cases in additive effects, with some supraadditive (PACAP(27) plus adrenaline) or subadditive (PACAP(38) or VIP plus noradrenaline) fluctuations. In contrast, combination of each of the three peptides with 3 muM forskolin resulted in synergistic effects. These results indicate that in rat cerebral cortex there is no synergism between PACAP or VIP with noradrenaline or adrenaline; however, based on the forskolin data, it seems likely that synergistic effects may take place with VIP or PACAP and other cAMP-stimulating neuroregulators.