The Influence of Calcium Channel Blockade L-Type on Colon Motility in Rats with Long-Term Adminis- tration of Omeprazole

Pilipenko S. V., Shelyuk О., Tseysler Yu., Nurishchenko N. Ye, Beregova T. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

The aim of the study was to investigate the colon motility and activities of Mg2 ± ,Ca2 ± ­ATPase and K ± (EGTA)­ATPase of actomyosin of colon smooth muscle in rats with long­term administration of omeprazole and after simultaneous injection of omeprazole and the blocker of calcium channel of L­type verapamile. The study was conducted on 60 white non­linear rats (180­200 g) were randomly divided into 3 groups. Animals of the 1st group (control) during 28 days were injected with 0,5 ml of H O intraperitoneally (i. p.). Animals of the 2nd group during 28 days were injected with inhibitor of н ± ­к ± ­ATPase omeprazole (14 mg/kg, i. p.) («Sigma­Aldrich», USA). The rats of the 3rd group during 28 days were injected with the same dose of omeprazole and the blocker of calcium channel of L­type verapamile (0,5 mg/kg, per os). In a day of last injection of drugs we investigated the colon motility in anesthetized rats by baloongraphic method and determined the activity of Mg2 ± ,Ca2 ± ­ATPase and K ± (EGTA)­ATPase of actomyosin of colon smooth muscle. It was established that after 28 days of blockade of gastric acid secretion in the rats by omeprazole frequency of spontaneous contractions in the colon unchanged, and the amplitude of spontaneous contractions and spontane­ ous motor activity index decreased by 66,5 % (p < 0,01) and 10,9 % (p < 0,05), respectively. Also colon motor activity induced carbacholin was significantly weakened: the amplitude of contractions decreased by 80 % (p < 0,01) and motor activity index diminished by на 20,3 % (p < 0,05). In the group of rats that within 28 days were administered simultaneously omeprazole and verapamil (the blocker of pH­sensitive receptor of G­cells which is calcium channel of L­type) spontaneous and stimulated colon motor activity was stronger compared to the group of rats which were administered omeprazole alone. But the motility parameters did not reach control values. The introduction of omeprazole to the rats during 28 days led to decrease of Mg2 ± ,Ca2 ± ­ATPase activity of actomyosin of colon smooth muscle by 58 % (p < 0,05) to compare with control. K ± (EGTA)­ATPase activity of actomyosin of colon smooth muscle also was diminished by 34 % (p < 0,05) in comparison with control. In the group of rats which were administered both omeprazole and verapamil Mg2 ± ,Ca2 ± ­ATPase activity of actomyosin of colon smooth muscle was at 18,5 % (p < 0,05) less than in controls. K ± (EGTA)­ATPase activity of ac­ tomyosin of colon smooth muscle enhanced to the control values. Thus, verapamil prevented the deep changes in ATPase activity of actomyosin of colon smooth muscle evoked by omeprazole. As a result, in this group of rats colon motility was better than in group of rats which were administered only omeprazole. Since verapamil significantly prevents the development of hypergastrinemia, we concluded that hypergastrinemia is one of the mechanisms of colon motility disturbances after prolonged administration of omeprazole . Conclusions. Long­term inhibition of gastric acid secretion by omeprazole evokes in the rats the decrease spon­ taneous and stimulated colon motility and also Mg2 ± ,Ca2 ± ­ATPase and K ± (EGTA)­ATPase activity of actomyosin of colon smooth muscle. Verapamil prevented the deep changes in colon motility and ATPase activity of actomyosin of colon smooth muscle evoked by omeprazole.

colon, motility, actomyosin, ATPase, оmeprazole, verapamil

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