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.
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D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009243:NAD / Q000494:pharmacology*; D009249:NADP / Q000494:pharmacology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011983:Receptors, Purinergic; D013565:Sympatholytics / Q000494:pharmacology
D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D013565:Sympatholytics; D009243:NAD; D001030:Apamin; D009249:NADP; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate