Mechanisms for regulation of gastrin and somatostatin release from isolated rat stomach during gastric distention.

AIM

To investigate the intragastric mechanisms for regulation of gastric neuroendocrine functions during gastric distention in isolated vascularly perfused rat stomach.

METHODS

Isolated vascularly perfused rat stomach was prepared, then the gastric lumen was distended with either 5,10 or 15 ml pH7 isotonic saline during a period of 20 min. During the distention, the axonal blocker tetrodotoxin (TTX), the cholinergic antagonist atropine, or the putative somatostatin-antagonist cyclo (7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)) were applied by vascular perfusion. The releases of gastrin and somatostatin were then examined by radioimmunoassay.

RESULTS

The graded gastric distention caused a significant volume-dependent decrease in gastrin secretion (-183+/-75 (5 ml), -385+/-86 (10 ml) and -440+/-85 (15 ml) pg/20 min) and a significant increase of somatostatin secretion (260+/-102 (5 ml), 608+/-148 (10 ml) and 943+/-316 (15 ml) pg/20 min). In response to 10 ml distention, the infusion of either axonal blocker TTX (10(-6) M) or cholinergic blocker atropine (10(-7) M) had a similar affect. They both attenuated the decrease of gastrin release by approximately 50 %, and attenuated the increase of somatostatin release by approximately 40 %. The infusion of somatostatin-antagonist cyclo (7-aminoheptanoyl-Phe-D-Trp-Lys-Thr (Bzl)) (10(-6)M) attenuated the decrease of gastrin release by about 60 %. Furthermore, combined infusion of the somatostatin-antagonist and atropine completely abolished distention-induced inhibition of gastrin release.

CONCLUSION

The present data suggest that distention of isolated rat stomach stimulates somatostatin release via cholinergic and non-cholinergic TTX-insensitive pathways. Both somatostatin and intrinsic cholinergic pathways are responsible for distention-induced inhibition of gastrin release.