Activation of the adenylyl cyclase/protein kinase A pathway facilitates neural release of beta-nicotinamide adenine dinucleotide in canine mesenteric artery

Abstract

Using high performance liquid chromatography techniques with fluorescence detection we demonstrate that overflow of beta-nicotinamide adenine dinucleotide evoked by electrical field stimulation (16 Hz, 0.3 ms) in the canine isolated mesenteric artery is increased by the activators of adenylyl cyclase (AC) forskolin and calcitonin gene-related peptide (CGRP), by dibutyryl cAMP, and by the inhibitors of phosphodiesterases III and IV milrinone and rolipram. The enhancing effect of forskolin is abolished by the AC inhibitor MDL 12,330A and by protein kinase A (PKA) inhibitors peptide 14-22 amide and 4-cyano-3-methylisoquinoline. Therefore, activation of the AC/cAMP/PKA pathway enhances the release of beta-NAD+ from perivascular nerve terminals.