Actions of adenine dinucleotides in the guinea‐pig taenia coli: NAD acts indirectly on P1purinoceptors; NADP acts like a P2‐purinoceptor agonist

Authors:
Open Access
Publisher website
Google Scholar
Abstract
The actions of the adenine dinucleotides β‐nicotinamide adenine dinucleotide (NAD) and β‐nicotinamide adenine dinucleotide phosphate (NADP) were examined on the carbachol‐contracted taenia coli of the guinea‐pig. Both were capable of inducing full relaxations in a concentration‐dependent manner; NADP was 21.4 times more effective than NAD at EC50; the threshold for NADP was approximately 0.1 μm and for NAD approximately 1.0 μm. The P1‐purinoceptor antagonist, 8‐phenyltheophylline (10 μm), produced a large parallel rightward shift in the NAD concentration‐response curve; in contrast it produced a small parallel leftward shift in the NADP concentration‐response curve. Dipyridamole (0.2 μm), a purine nucleoside uptake inhibitor, markedly potentiated responses to NAD and slightly potentiated NADP. 8‐Phenyltheophylline antagonized the dipyridamole potentiation of both NAD and NADP. By use of high performance liquid chromatography it was shown that the action of NAD involves a breakdown to adenosine. Apamin, a K+ channel blocker, which antagonizes P2‐purinoceptor activation in the intestine, abolished responses to NADP but not to NAD. The α‐ and β‐adrenoceptor antagonists, phentolamine (1 μm) and propranolol (1 μm), did not affect responses to NAD or NADP. Tetrodotoxin, a neurotoxin, did not abolish responses to either NAD or NADP. It is concluded that NAD acts largely indirectly as a P1‐purinoceptor agonist following its breakdown to adenosine by ectoenzymes, while NADP acts in a similar manner to a P2‐purinoceptor agonist.
Keywords

This publication has 26 references indexed in Scilit: