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 electrically-induced nonadrenergic noncholinergic (NANC) motor activity with special interest in the apamin-sensitive mechanisms was studied in a guinea pig ileum model. Depending on the concentration (0.1 or 1 micromol/l), apamin, a blocker of the calcium-activated potassium channels and antagonist of ATP action, induced either TTX (0.1 micromol/l)-resistant increase in tone or contractions. SNP, a nitric oxide donor, applied cumulatively (0.1-100 micromol/l) evoked a concentration-dependent relaxation, the EC50 value being 0.39 +/- 0.12 micromol/l. At concentrations of 0.1 or 1 micromol/l, apamin decreased the SNP effects and shifted the concentration-response curves for SNP to the right. The EC50 value for SNP in the presence of apamin at a concentration of 0.1 micromol/l increased to 59.34 +/- 36.53 micromol/l. ATP (1 or 50 micromol/l) induced TTX-resistant contractions. The effects of ATP were reduced by apamin (1 micromol/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 and tonic. L-NNA (0.5 mmol/l), an inhibitor of nitric oxide syntheses, abolished the relaxation phase. L-arginine (0.5 mmol/l) restored it. Apamin (0.1 or 1 micromol/l) completely eliminated the relaxation phase and concentration-dependently inhibited the tonic contraction of the phase of contractions. The present findings indicate that the apamin-sensitive nitric oxide-evoked relaxation could be realized by calcium-activated potassium channels and that the apamin-sensitive ATP-induced contraction is mediated via contraction-producing P2 purinoceptors.
Ivancheva
C
C
Laboratory Peripheral Synapses, Bulgarian Academy of Sciences, Sofia.
Rahamimoff
R
R
Radomirov
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019335:Nitroarginine; D001030:Apamin; D009569:Nitric Oxide; D000255:Adenosine Triphosphate