Apamin-sensitive nitric oxide- and ATP-mediated motor effects on the guinea pig small intestine

The involvement of nitric oxide and ATP in both spontaneous and electricall y-induced nonadrenergic noncholinergic (NANC) motor activity with special i nterest in the apamin-sensitive mechanisms was studied in a guinea pig ileu m model. Depending on the concentration (0.1 or 1 mu mol/l), apamin, a bloc ker of the calcium-activated potassium channels and antagonist of ATP actio n, induced either TTX (0.1 mu mol/l)-resistant increase in tone or contract ions. SNP, a nitric oxide donor, applied cumulatively (0.1-100 mu mol/l) ev oked a concentration- dependent relaxation, the EC50 value being 0.39 +/- 0 .12 mu mol/l. At concentrations of 0.1 or 1 mu mol/l, apamin decreased the SNP effects and shifted the concentration-response curves for SNP to the ri ght. The EC50 value for SNP in the presence of apamin at a concentration of 0.1 mu mol/l increased to 59.34 +/- 36.53 mu mol/l. ATP (1 or 50 mu mol/l) induced TTX-resistant contractions. The effects of ATP were reduced by apa min (1 mu mol/l). The contractile effect of ATP occurred in the presence of SNP. SNP provoked relaxation on the background of ATP. The NANC responses to electrical stimulation (0.8 ms, 40 V, 2 or 20 Hz, 20 s) consisted of an initial relaxation phase followed by a phase of contractions, twitch-like a nd tonic. L-NNA (0.5 mmol/l), an inhibitor of nitric oxide syntheses, aboli shed the relaxation phase. L-arginine (0.5 mmol/l) restored it. Apamin (0.1 or 1 mu mol/l) completely eliminated the relaxation phase and concentratio n-dependently inhibited the tonic contraction of the phase of contractions. The present findings indicate that the apamin-sensitive nitric oxide-evoke d relaxation could be realized by calcium-activated potassium channels and that the apamin-sensitive ATP-induced contraction is mediated via contracti on-producing P-2 purinoceptors.