PHYSIOLOGY AND PHARMACOLOGY OF NEUROPEPTIDES

蛙皮素对胃液分泌的中枢神经调节作用(和 蛙皮素相关多肽)和新的拟吗啡多肽 以实验大鼠为模型系统进行了研究。这个 脑室注射蛙皮素的调节作用 幽门结扎大鼠的胃分泌物；中和胃酸， 降低氢离子浓度，减少分泌量。 只有与蛙皮素非常相似的多肽，如alytesin和grp (哺乳动物类似蛙皮素的七肽)也有类似的 生物活性。前列腺素的强效抑制剂吲哚美辛 生物合成，在给药时阻止蛙皮素介导的效应 ICV。这些结果表明，胃分泌物的神经调节是通过 蛙皮素与前列腺素在大脑中的释放有关。去吗啡，一种 含有天然D-氨基酸的两栖类鸦片状七肽， 脑室给药时有效减少胃液分泌。分析 19种德吗啡的同系物和类似物为 胃酸输出神经调节的序列特异性。这个 氨基末端四肽酰胺提供的生物活性最小 片断(类似于大脑中德吗啡的极限消化产物 匀浆)。丙氨酸2位残基的D-异构体是不可缺少的 以保持生物活性。地吗啡用于治疗的剂量 抑制胃液分泌不仅对止痛没有影响，而且 类似物也表现出不同的效应。 这些生理参数。因此，德吗啡在大脑的 大脑，可能与Mu受体或其亚型相互作用， 调节胃液分泌。

The central neuromodulation of gastric secretion by bombesin (and bombesin-related peptides) and the new morphinomimetic peptide dermorphin were investigated using the laboratory rat as the model system. The intracerebral ventricular (icv) administration of bombesin regulates gastric secretion in pylorus-ligated rats; neutralizes gastric acidity, reduces hydrogen ion concentration, and decreases the volume of secretion. Only peptides closely resembling bombesin, such as alytesin and GRP (mammalian heptacosapeptide resembling bombesin) had comparable bioactivity. Indomethacin, a potent inhibitor of prostaglandin biosynthesis, prevented the bombesin-mediated effects when administered icv. These results suggest that the neuromediation of gastric secretion by bombesin involves the release of prostaglandins in brain. Dermorphin, an amphibian opiate-like heptapeptide containing a natural D-amino acid, effectively reduces gastric secretion when administered icv. The analysis of 19 homologues and analogues of dermorphin provided evidence on the sequence specificity of the neuroregulation of gastric acid output. The amino-terminal tetrapeptide amide provided the smallest biological active fragment (similar to the limit digestion product of dermorphin in a brain homogenate). The D-isomer of Ala residue at position 2 is indispensible for the retention of bioactivity. The dosages of dermorphin utilized to suppress gastric secretion were not only without effect on analgesia or catalepsy, but also the analogues displayed differential effects in respect to these physiological parameters. Thus, dermorphin acts centrally in the brain, presumably interacting with either mu receptors, or subtype thereof, to regulate gastric secretion.