Excitatory effect of P2X receptor activation on mesenteric afferent nervesin the anaesthetised rat

1. We examined the effects of P2X purinoceptor agonists and P2 purinoceptor antagonists on mesenteric afferent nerves supplying the jejunum in the pen tobarbitone sodium-anaesthetised rat. 2. ATP (0.01-10 mg kg(-1), I.A.) and alpha,beta-methylene-ATP (1-30 mu g kg (-1) I.A.) each induced dose-dependent increases in afferent nerve discharg e and intrajejunal pressure. The effect on afferent nerves comprised an ear ly (< 2 s after administration) intense burst of activity followed by a lat er increase (> 2 s after administration), less pronounced in comparison, wh ich coincided with elevated intrajejunal pressure. 3. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (20 mg kg(-1) I.V. ) and suramin (80 mg kg(-1), I.V.) each antagonised both the early and late r increases in afferent nerve discharge elicited by alpha,beta-methylene-AT P (30 mu g kg(-1), I.A). 4. Co-administration of omega-conotoxin MVIIS and omega-conotoxin SVIB (eac h at 25 mu g kg(-1), I.V.), or treatment with the selective 5-HT3 receptor antagonist alosetron (30 mu g kg(-1), I.V.), did not affect the rapid burst of afferent nerve activity elicited by alpha,beta-methylene-ATP (30 mu g k g(-1), I.A.). However, toxin treatment did attenuate the elevations in intr ajejunal pressure and the corresponding later phases of evoked afferent dis charge, while alosetron inhibited basal afferent nerve activity. 5. In summary, ATP and alpha,beta-methylene-ATP each evoke excitation of me senteric afferent nerves in the anaesthetised rat. We propose that the earl y increase in mesenteric afferent nerve activity represents a direct effect on the nerve ending, mediated by P2X receptors, whereas the later increase reflects activation of mechanosensitive fibres secondary to elevated intra jejunal pressure.