Nitrergic and purinergic interplay in inhibitory transmission in rat gastric fundus

1 This study was undertaken to analyse the involvement of ATP in non-adrenergic non- cholinergic (NANC) relaxation and possible interplay between nitrergic and purinergic systems in rat gastric fundus. 2 Experiments were performed in vitro on strips of longitudinal muscle from rat gastric fundus, recording the mechanical activity as changes in isometric force. In addition, NO release induced by different experimental conditions was assayed. 3 Under NANC conditions in serotonin-precontracted strips, electrical field stimulation (EFS) elicited a tetrodotoxin (TTX)-sensitive relaxation accompanied by nitric oxide (NO) release. This effect was antagonized by pretreatment with the NO synthase antagonist Nomega-nitro-L-arginine (L-NA) or by desensitization of purinergic receptors. Purinergic desensitization was also able to further antagonize the residual EFS-induced relaxation remaining after L-NA treatment. Exogenously applied NO [delivered as sodium nitroprusside (SNP)] or ATP (and related purines) induced concentration-dependent, TTX-insensitive relaxant responses. ATP also induced the release of NO. A reduction in the responses to ATP was observed in the presence of L-NA. In contrast, SNP-induced relaxation remained unchanged after desensitization of purinergic receptors. Finally, apamin, a blocker of the small conductance Ca2+ -dependent K+ channels, reduced the amplitude of the muscular relaxation evoked by either EFS, ATP or SNP. 4 In conclusion, this study provides evidence that in rat gastric fundus, ATP is one of the inhibitory transmitters released from NANC intramural neurones acting directly on the muscle, through receptors coupled to apamin-sensitive Ca2+ -dependent K+ channels and, indirectly, through the stimulation of NO production.