Dembiński A, Warzecha Z, Konturek S J, Cai R Z, Schally A V
Institute of Physiology Academy of Medicine, Kraków, Poland.
J Physiol Pharmacol. 1991 Jun;42(2):195-209.
The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718 a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365,260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptor but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.
在禁食48小时的大鼠以及再喂食16小时（无论是否给予蛙皮素、胃泌素和胆囊收缩素的特异性受体拮抗剂）的大鼠中，研究了胃泌素、胆囊收缩素（CCK）和蛙皮素对DNA合成的影响，DNA合成作为胃十二指肠黏膜和胰腺营养作用的生化指标。在禁食大鼠中，每天三次给予蛙皮素和胃泌素，持续48小时，通过检测[3H]胸腺嘧啶掺入各测试组织DNA的情况来衡量，结果显示DNA合成速率显著增加。CCK显著增加十二指肠黏膜和胰腺组织中的DNA合成，但对胃黏膜无此作用。蛙皮素/胃泌素释放肽（GRP）受体拮抗剂RC-3095可消除蛙皮素对胃十二指肠黏膜和胰腺中DNA合成的刺激作用。RC-3095不影响胃泌素和CCK对这些组织中DNA合成的刺激。胃泌素受体拮抗剂L-365,260可抑制胃泌素诱导的胃肠道黏膜和胰腺中的DNA合成，但不影响CCK或蛙皮素诱导的DNA合成。CCK受体特异性拮抗剂L-364,718仅对CCK刺激的十二指肠黏膜和胰腺生长有效。对禁食48小时的大鼠再喂食可强烈增强所有测试组织中的DNA合成，仅阻断胃泌素受体（使用L-365,260）可显著降低胃十二指肠黏膜中的这种作用，而拮抗CCK受体（使用L-364,718）可降低十二指肠黏膜和胰腺中的这种作用。拮抗蛙皮素受体（使用RC-3095）对再喂食诱导的所有测试组织中DNA合成的刺激作用无显著影响。本研究表明，外源性胃泌素、CCK和蛙皮素通过各自独立的受体可实现对DNA合成的刺激，但仅胃泌素和CCK在餐后刺激胃十二指肠黏膜和胰腺组织生长中起主要作用。
