Activation of the adenylyl cyclase/protein kinase A pathway facilitates neural release of beta-nicotinamide adenine dinucleotide in canine mesenteric artery.
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.
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557-0271, USA.
Janette
J
Bobalova
Violeta N
VN
Mutafova-Yambolieva
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004285:Dogs; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D020105:Milrinone / Q000494:pharmacology; D009243:NAD / Q000378:metabolism*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
C511972:4-cyano-3-methylisoquinoline; D000067956:Adenylyl Cyclase Inhibitors; D007097:Imines; D007546:Isoquinolines; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D009243:NAD; D005576:Colforsin; D003994:Bucladesine; C014925:RMI 12330A; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D015740:Calcitonin Gene-Related Peptide; D020105:Milrinone; D020889:Rolipram