Accumulation of Cyclic AMP Elicited by Vasoactive Intestinal Peptide Is Potentiated by Noradrenaline, Histamine, Adenosine, Baclofen, Phorbol Esters, and Ouabain in Mouse Cerebral Cortical Slices: Studies on the Role of Arachidonic Acid Metabolites and Protein Kinase C

Abstract: In mouse cerebral cortical slices, noradrenaline (NA) potentiates cyclic AMP (cAMP) accumulation elicited by vasoactive intestinal peptide (VIP) through α₁‐adrenergic receptors. This synergism is inhibited by indomethacin, and the prostaglandins E₂ and F_2α mimic the effect of NA. In the present study, we observed that the synergism between VIP and NA is not inhibited by the protein kinase C inhibitor 1‐(5‐isoquinolinylsulfonyI)‐2‐methylpiperazine (H‐7) or the diacylglycerol‐lipase inhibitor RHC 80267, thus further stressing the role of phospholipase A₂ activation. Various neuroactive agents that potentiate the stimulatory effect of VIP on cAMP formation were also examined. As with NA, the potentiation by histamine and adenosine is inhibited by indomethacin. In contrast to NA, histamine, and adenosine, the synergistic interaction between phorbol esters and VIP on cAMP formation is abolished by H‐7 but not by indomethacin. The potentiation by baclofen, a y‐aminobutyric acid_B receptor agonist, is partially inhibited by the 5‐lipox‐ygenase inhibitor nafazatrom. The synergism between ouabain and VIP is reduced by H‐7 but not by indomethacin and nafazatrom. These data indicate that the stimulation of cAMP formation elicited by VIP is under the modulation of various neuroactive agents that trigger diverse intracellular mechanisms to potentiate the effect of the peptide.