PHYSIOLOGY AND PHARMACOLOGY OF NEUROPEPTIDES

肽对外周事件的中枢调节 激素是一个相对较新的领域。 脑室内 (icv)施用蛙皮素、皮吗啡肽（蛙皮衍生的 鸦片七肽），降钙素（鲑鱼）和锂（药物的 选择躁狂抑郁症）有效地减少了所有 幽门结扎禁食大鼠的胃分泌参数： 中和的酸性pH，降低的氢离子浓度，和 胃分泌物量减少。 然而，在这方面， 这些肽的皮下（sc）注射产生了不同的 相对于icv的作用：蛙皮素活性很弱 （无剂量-反应曲线），而皮吗啡为0.0003， 强有力的;降钙素，另一方面，表现出两倍的 活动sc作为icv。 氯化锂对icv和 sc，尽管sc的降低响应与 稀释锂在整个身体。 蛙皮素和 锂似乎起着中心作用，也许是通过一个共同的 机制，通过花生四烯酸产物对胃分泌的影响 代谢（例如，因为它们的效果可以是 被几种环氧合酶抑制剂（吲哚美辛， 双氯芬酸、萘普生、酮洛芬）。 锂和蛙皮素， 产生类似的效果，并涉及到兰丁，这样做， 通过不同的途径;下丘脑中的蛙皮素水平 不受ICV给药锂的影响。 几个二聚体 皮吗啡肽的类似物（2条皮吗啡肽链通过 C-末端酰胺氮直接或通过 亚甲基桥）测试它们抑制 并将该效应与分析 大脑突触体中的δ和μ受体。 只有那些 显示μ-选择性的类似物在体内是有活性的， 对胃分泌生物活性谱不同于 皮吗啡 尽管皮吗啡需要中枢μ-型 阿片受体的胃分泌，降钙素的作用是 不太清楚，可能涉及多种相互作用的机制。

The central neuroregulation of peripheral events by peptide hormones is a relatively new field. The intracerebral ventricular (icv) administration of bombesin, dermorphin (a frog-skin derived opiate heptapeptide), calcitonin (salmon) and lithium (the drug of choice for manic depression) effectively decreased all parameters of gastric secretion in pylorus-ligated fasted rats: neutralized acidic pH, reduced hydrogen ion concentration, and decreased volume of stomach secretions. However, subcutaneous (sc) injections of these peptides yielded differential effects relative to icv: bombesin was very weakly active (without a dose-response curve), while dermorphin was 0.0003 as potent; calcitonin, on the other hand, exhibited twice the activity sc as icv. Lithium chloride was effective both icv and sc, although the reduced response by sc is in keeping with the dilution of lithium throughout the body. Both bombesin and lithium appear to act centrally, perhaps through a common mechanism, on gastric secretion via products of arachidonate metabolism (e.g., prostaglandins) since their effects can be blocked by several cyclooxygenase inhibitors (indomethacin, diclofenac, naproxen, ketoprofen). Lithium and bombesin, which produce a similar effect and involve prostaglandins, do so through different routes; bombesin levels in the hypothalamus are unaffected by icv administered lithium. Several dimeric analogues of dermorphin (2 chains of dermorphin linked though the C-terminal amide nitrogen either directly or through methylene bridges) were tested for their ability to suppress gastric secretion and correlate that effect with an analysis of delta and mu receptors in brain synaptosomes. Only those analogues exhibiting mu-selectivity were active in vivo and their spectrum of bioactivity on gastric secretion were distinct from dermorphin. Although dermorphin requires central mu-type opiate receptors for gastric secretion, the role of calcitonin is less clear and may involve multiple interacting mechanisms.