The reactivity of serotonin, acetylcholine and kcl-induced contractions to relaxant agents in the rat gastric fundus.

The effects of nifedipine, cromakalim, diazoxide, caffeine and sodium nitroprusside (SNP) on acetylcholine, serotonin and KCl-induced contractions were studied in rat stomach fundus. Thus, we aimed to demonstrate how these contractions are modified by the substances acting on Ca (2+)influx and intracellular Ca (2+)stores. Serotonin (10(-9) - 10(-5) M) and KCl (20-80 mM) showed a similar contraction profile, which was slightly different from that of acetylcholine (10(-8)- 3 x 10(-3) M). In the experiments with the incubation of calcium-free/EGTA (0.5 mM) Krebs solution for 20 min, serotonin (3 x 10(-7)M) and KCl (40 mM) did not produce any contraction whereas, 10% of contraction to acetylcholine (3 x 10(-5) M) was still intact. Serotonin-induced contractions were readily reversed by nifedipine (10(-10) - 10(-4) M), cromakalim (10(-9) - 10(-4) M), diazoxide (10(-9) - 10(-4) M), caffeine (10(-5) - 10(-2) M) and SNP (10(-4) M) whereas, acetylcholine-induced contractions showed relative refractoriness to the above relaxant agents. 1 mM caffeine nearly fully inhibited serotonin-induced contraction, but not acetylcholine and high K-induced contractions whereas, 10 mM caffeine completely inhibited all the contractions. The relaxation pattern of nifedipine on serotonin and high K (+)-induced contractions was quite similar. Moreover, nifedipine and cromakalim showed equal dose effectiveness in relaxing acetylcholine and serotonin. The maximum relaxations induced by nifedipine and cromakalim in acetylcholine contractions were 61.51 +/- 6.92 % and 58.97 +/- 7.55 %, respectively. However their maximum relaxations in serotonin and high K (+)-induced contractions were almost 100%. The similarity in myorelaxants properties of cromakalim and nifedipine may relate to the similarity of their effects on calcium influx by a different mechanism of action in rat stomach fundus. In conclusion, acetylcholine-induced contraction is partially mediated both by calcium release from the intracellular Ca (2+) pool and calcium influx via L-type Ca (2+) channels. However, serotonin-induced contraction is possibly triggered by Ca (2+) release from sarcoplasmic reticulum and basically mediated by Ca (2+) influx via L-type Ca (2+)channels. Copyright 2002 Published by Elsevier Science Ltd.