Rowland N E, Caputo F A, Fregly M J
Brain Res Bull. 1987 Apr;18(4):501-8. doi: 10.1016/0361-9230(87)90115-8.
The present studies were designed to investigate further the mechanism by which water intake is induced in rats by peripheral administration of either serotonin (5HT) or its precursor 5-hydroxytryptophan (5HTP). Consistent with previous studies that have implicated mediation by the renal renin-angiotensin system (RAS), we now report that bilateral nephrectomy completely abolishes the drinking response to various doses of 5HT. In contrast, nephrectomy had little effect on the drinking induced by 5HTP. Thus, 5HTP may induce drinking by mechanisms other than its peripheral conversion to 5HT and subsequent activation of the RAS. The drinking responses to both 5HT and 5HTP were blocked by peripheral administration of the 5HT receptor antagonist, metergoline, but the drug was at least ten-fold more potent against 5HTP than 5HT. Intracerebroventricular (ICV) administration of metergoline also prevented the drinking response to peripherally-administered 5HTP. The drinking responses to both 5HT and 5HTP were enhanced by peripheral administration of low doses of an angiotensin I converting enzyme inhibitor, captopril. Collectively, these findings support previous conclusions that 5HT-induced intake of water is mediated exclusively by the renal RAS. However, 5HTP-induced drinking may additionally involve a renin-independent, serotonin-mediated mechanism, possibly in the brain.
本研究旨在进一步探究通过外周给予血清素（5-羟色胺，5HT）或其前体5-羟色氨酸（5HTP）诱导大鼠饮水的机制。与先前涉及肾素-血管紧张素系统（RAS）介导作用的研究一致，我们现在报告双侧肾切除完全消除了对各种剂量5HT的饮水反应。相比之下，肾切除对5HTP诱导的饮水影响很小。因此，5HTP可能通过其外周转化为5HT并随后激活RAS以外的机制诱导饮水。外周给予5HT受体拮抗剂美替拉酮可阻断对5HT和5HTP的饮水反应，但该药物对5HTP的效力比对5HT至少强十倍。脑室内（ICV）给予美替拉酮也可防止对外周给予的5HTP的饮水反应。外周给予低剂量的血管紧张素I转换酶抑制剂卡托普利可增强对5HT和5HTP的饮水反应。总体而言，这些发现支持先前的结论，即5HT诱导的饮水完全由肾RAS介导。然而，5HTP诱导的饮水可能还涉及一种不依赖肾素、由血清素介导的机制，可能发生在大脑中。
