Jensen R T
National Institutes of Health, Bethesda, Maryland 20892-1804, USA.
Yale J Biol Med. 1996 May-Jun;69(3):245-59.
Cholecystokinin (CCK) and the structurally related peptide, gastrin, have numerous effects on tissues in the central nervous system and gastrointestinal tract. Recent studies show these effect are mediated by a CCKA and CCKB receptor. Knowledge of the physiological role and role of CCKB receptors in pathologic processes has been particularly limited by the availability of selective, potent receptor antagonists. Recently, new members of five different classes of non-peptide CCKB receptor antagonists are reported and are reviewed briefly. these include compounds isolated from Streptomyces (tetronothiodin, virginiamycin analogues), ureido-acetamide analogues (RP 69758, RP 72540, RP 73870), newer benzodiazepine analogues (L-368,935, L-740,093, YM022), pyrazolidimine analogues (LY 262,691) and glutamic acid analogues (CR2194). Many of these compounds have greater than 1000-fold selectivity for the CCKB over the CCKA receptor and some have greater than 10,000-fold selectivity. The pharmacology and effects of CCKB receptor antagonists on gastric acid secretion is briefly reviewed. Furthermore, the possible clinical usefulness of CCKB receptor antagonists in treating disorders of gastric acid secretion, in inhibiting the trophic effects of gastrin and in other clinical conditions is briefly discussed.
胆囊收缩素（CCK）以及结构相关肽胃泌素，对中枢神经系统和胃肠道的组织有多种作用。最近的研究表明，这些作用是由CCKA和CCKB受体介导的。由于缺乏选择性、强效的受体拮抗剂，CCKB受体在病理过程中的生理作用和作用一直受到特别限制。最近，报道了五种不同类别的非肽CCKB受体拮抗剂的新成员，并对其进行了简要综述。这些包括从链霉菌中分离出的化合物（硫代四肽菌素、维吉尼亚霉素类似物）、脲基乙酰胺类似物（RP 69758、RP 72540、RP 73870）、新型苯二氮卓类似物（L-368,935、L-740,093、YM022）、吡唑并二亚胺类似物（LY 262,691）和谷氨酸类似物（CR2194）。这些化合物中的许多对CCKB受体的选择性比对CCKA受体高1000倍以上，有些则具有超过10000倍的选择性。简要综述了CCKB受体拮抗剂对胃酸分泌的药理学和作用。此外，还简要讨论了CCKB受体拮抗剂在治疗胃酸分泌紊乱、抑制胃泌素的营养作用及其他临床病症方面可能的临床应用价值。
