Evidence that adenosine 5′‐triphosphate is the third inhibitory non‐adrenergic non‐cholinergic neurotransmitter in the rat gastric fundus

In the rat gastric fundus, non-adrenergic, non-cholinergic (NANC) relaxations are mediated by nitric oxide (NO), vasoactive intestinal polypeptide (VIP), and a third, as yet unidentified, neurotransmitter. The possible involvement of adenosine 5′-triphosphate (ATP) in the NANC relaxations was examined using pyridoxalphosphate-6-azophenyl-2′,5′-disulphonic acid (PPADS), apamin and desensitization to α,β-methylene ATP. NANC responses were studied in the absence and presence of NG-nitro-L-arginine methyl ester (NAME; 100 μM) and α-chymotrypsin (1 u ml−1), to inhibit responses to NO and VIP, respectively. PPADS (100 μM), apamin (1 μM) and desensitization to α,β-methylene ATP (10 μM, three additions) all significantly (P<0.05) reduced NANC relaxations to electrical field stimulation (0.5–4 Hz, 30 s trains) in longitudinal strips of rat gastric fundus and almost abolished the residual relaxation remaining in the presence of NAME and α-chymotrypsin. PPADS had no effect on responses to the NO-donor, sodium nitroprusside (SNP), or VIP. Apamin slightly reduced relaxations to SNP, but did not affect those to VIP, whereas desensitization to α,β-methylene ATP markedly reduced responses to both SNP and VIP. The effects of PPADS and apamin in this study provide strong evidence that the third inhibitory NANC neurotransmitter in the rat gastric fundus is ATP. British Journal of Pharmacology (2000) 130, 1627–1631; doi:10.1038/sj.bjp.0703481