Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, Sahlgrenska University Hospital, Gothenburg, Sweden.
PLoS One. 2013 Aug 15;8(8):e72347. doi: 10.1371/journal.pone.0072347. eCollection 2013.
Cocaine- and amphetamine-regulated transcript peptides (CARTp) suppress nutritional intake after administration into the fourth intracerebral ventricle. Recent in vitro studies have shown that PACAP 6-38, a pituitary adenylate cyclase-activating polypeptide (PACAP) fragment, could act as a competitive antagonist against CARTp 55-102 on a common CARTp-sensitive receptor structure. Here, we show for the first time in vivo that the reduction in solid food intake induced by exogenous CARTp 55-102 (0.3 nmol: 1.5 µg) administered fourth i.c.v. is blocked by pretreatment with PACAP 6-38 (3 nmol). The PACAP 6-38 fragment had no effect by itself either when given into the fourth ventricle or subcutaneously. Although effective to block the CARTp-effect on feeding and short-term body weight, PACAP 6-38 failed to attenuate CARTp-associated gross motor behavioral changes suggesting at least two CARTp-sensitive receptor subtypes. In conclusion, PACAP 6-38 acts as a functional CARTp antagonist in vivo and blocks its effects on feeding and short term weight gain.
可卡因和苯丙胺调节转录肽（CARTp）在第四脑室内给药后抑制营养摄入。最近的体外研究表明，PACAP 6-38，一种垂体腺苷酸环化酶激活肽（PACAP）片段，可作为 CARTp 55-102 对共同的 CARTp 敏感受体结构的竞争性拮抗剂。在这里，我们首次在体内显示，外源性 CARTp 55-102（0.3 nmol：1.5 µg）经第四脑室内给药引起的固体食物摄入减少被 PACAP 6-38（3 nmol）预处理阻断。PACAP 6-38 片段本身无论是在第四脑室还是皮下给药都没有效果。虽然 PACAP 6-38 有效阻断 CARTp 对摄食和短期体重的影响，但未能减轻 CARTp 相关的大体运动行为变化，这表明至少存在两种 CARTp 敏感受体亚型。总之，PACAP 6-38 在体内作为 CARTp 的功能性拮抗剂，阻断其对摄食和短期体重增加的作用。
