Leibowitz S F, Kim T
Rockefeller University, New York, NY 10021.
Brain Res. 1992 Dec 18;599(1):148-52. doi: 10.1016/0006-8993(92)90863-5.
The peptide galanin (GAL) has a potent stimulatory effect on fat ingestion after administration into the hypothalamic paraventricular nucleus (PVN). This study examined a newly synthesized GAL antagonist, M40, in two separate experiments involving: (1) PVN injections of M40 alone in freely feeding animals, to investigate the importance of endogenous GAL receptor activity in determining natural patterns of fat ingestion, and (2) PVN injections of M40 in combination with exogenous GAL, to determine whether endogenous GAL receptors mediate this peptide-induced response. The results demonstrate that PVN injection of M40 by itself dose-dependently (2-108 pmol) reduces spontaneous ingestion of the fat diet. This phenomenon is robust, behaviorally specific and opposite to that induced by GAL itself. Moreover, the stimulatory effect of PVN-injected GAL on fat ingestion can be blocked by prior PVN administration of M40 at relatively low doses (2-6 pmol), indicating that M40 is a potent antagonist of GAL receptors in the hypothalamus. Together, these results provide the first evidence for the existence of endogenous GAL receptors in mediating the action of exogenous GAL in the hypothalamus. They also constitute a crucial step in demonstrating a physiological function of these PVN GAL receptors in controlling natural patterns of fat ingestion.
将肽类物质甘丙肽（GAL）注入下丘脑室旁核（PVN）后，对脂肪摄取具有强大的刺激作用。本研究在两项独立实验中检测了一种新合成的GAL拮抗剂M40，实验包括：（1）在自由进食的动物中单独向PVN注射M40，以研究内源性GAL受体活性在决定脂肪摄取自然模式中的重要性；（2）将M40与外源性GAL联合注入PVN，以确定内源性GAL受体是否介导这种肽诱导的反应。结果表明，单独向PVN注射M40（2 - 108皮摩尔）可剂量依赖性地减少脂肪饮食的自发摄取。这种现象强烈、行为特异，且与GAL本身诱导的现象相反。此外，在相对低剂量（2 - 6皮摩尔）下，预先向PVN注射M40可阻断向PVN注射GAL对脂肪摄取的刺激作用，表明M40是下丘脑GAL受体的有效拮抗剂。总之，这些结果首次证明了内源性GAL受体在介导下丘脑中外源性GAL作用方面的存在。它们也构成了证明这些PVN GAL受体在控制脂肪摄取自然模式中的生理功能的关键一步。
