Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Burnstock, G. et al.

Actions of adenine dinucleotides in the guinea-pig taenia coli: NAD acts indirectly on P1-purinoceptors; NADP acts like a P2-purinoceptor agonist.

The actions of the adenine dinucleotides beta-nicotinamide adenine dinucleotide (NAD) and beta-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 microM and for NAD approximately 1.0 microM. The P1-purinoceptor antagonist, 8-phenyltheophylline (10 microM), 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 microM), a purine nucleoside uptake inhbitor, 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 alpha-and beta-adrenoceptor antagonists, phentolamine (1 microM) and propranolol (1 microM), 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.[1]

References

Actions of adenine dinucleotides in the guinea-pig taenia coli: NAD acts indirectly on P1-purinoceptors; NADP acts like a P2-purinoceptor agonist. Burnstock, G., Hoyle, C.H. Br. J. Pharmacol. (1985) [Pubmed]

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