Metabolic Actions of the Type 1 Cholecystokinin Receptor: Its Potential as a Therapeutic Target

被引：33

作者：

Miller, Laurence J. ^{[1
]}

Desai, Aditya J. ^{[1
]}

机构：

[1] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Scottsdale, AZ 85259 USA

来源：

TRENDS IN ENDOCRINOLOGY AND METABOLISM | 2016年 / 27卷 / 09期

关键词：

VAGAL AFFERENT NEURONS; HUMAN CCK1 RECEPTOR; INTERMEAL INTERVAL; FOOD-INTAKE; MOLECULAR-BASIS; BINDING-SITE; MEAL SIZE; ENDOGENOUS CHOLECYSTOKININ; PANCREATIC-POLYPEPTIDE; GASTROINTESTINAL SITES;

D O I：

10.1016/j.tem.2016.04.002

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Cholecystokinin (CCK) regulates appetite and reduces food intake by activating the type 1 CCK receptor (CCK1R). Attempts to develop CCK1R agonists for obesity have yielded active agents that have not reached clinical practice. Here we discuss why, along with new strategies to target CCK1R more effectively. We examine signaling events and the possibility of developing agents that exhibit ligand-directed bias, to dissociate satiety activity from undesirable side effects. Potential allosteric sites of modulation are also discussed, along with desired properties of a positive allosteric modulator (PAM) without intrinsic agonist action as another strategy to treat obesity. These new types of CCK1R-active drugs could be useful as standalone agents or as part of a rational drug combination for management of obesity.

引用

页码：609 / 619

页数：11

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