NAD‐evoked responses in porcine isolated mesenteric arteries

Nicotinamide adenine dinucleotide (NAD) is an “intracellular” nucleotide derivative, which has also been identified as an agonist for P2Y 1 receptors (Mutafova‐Yambolieva, 2007), P2X receptors (Grahnert, 2009) and adenosine receptors (Hoyle, 1990). The present study investigated responses evoked by NAD in porcine isolated mesenteric arteries precontracted with U46619 (10–100 nM). In isometric tension recordings, NAD (10 −7 –10 −3 M) evoked concentration‐dependent contractions of the U46619‐pre‐contracted porcine mesenteric artery with a maximal response of 43 ± 6% U46619‐induced tone and p EC 50 value of 4.5 ± 0.3; these contractions were unaltered in the presence of palmitoyl CoA (10 μM, a P2Y 1 receptor antagonist), CGS15943 (10 μM, a non‐selective adenosine receptor antagonist), SCH58261 (100 nM, a selective A 2A adenosine receptor antagonist) or suramin (100 μM, a non‐selective P2 receptor antagonist). In contrast, α,β‐methylene ATP (10 μM, a desensitizing P2X receptor agonist) significantly reduced these responses (maximal response of 17 ± 8 % and p EC 50 value of 5.0 ± 0.4). Endothelium removal had no significant effect on the NAD‐induced contractions. We conclude that NAD‐evoked contractions in the porcine mesenteric artery are mediated by actions on the smooth muscle and do not involve P1 or P2Y 1 receptors. The effect of α,β‐methylene ATP on these responses suggests the involvement of suramin‐insensitive P2X 1 ‐like receptors. We gratefully acknowledge and appreciate the sponsorship of the Jordanian government.