Department of Basic Veterinary Science, Laboratory of Physiology, Joint Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
Division of Biological Principles, Department of Physiology and Biophysics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan.
J Physiol Sci. 2024 Nov 22;74(1):54. doi: 10.1186/s12576-024-00949-w.
We investigated the effects of a centrally penetrant ghrelin agonist, RQ-00538053, on colorectal motility in female rats in comparison with that in male rats. Intravenous administration of RQ-00538053 enhanced colorectal motility in female rats. However, approximately tenfold higher doses were required to induce responses in female rats similar to those in male rats. Higher doses were required even when the agonist was intrathecally administered to the lumbosacral spinal cord in female rats. The results of RT-qPCR showed that the level of ghrelin receptor expression in the lumbosacral spinal cord was lower in female rats than in male rats, suggesting that the lower expression level of the receptor may contribute, at least in part, to the sex differences in the action of RQ-00538053. The sexually dimorphic action of a ghrelin agonist will be important for future works aiming to utilize ghrelin agonists as novel drugs to improve constipation.
我们研究了一种中枢穿透性胃饥饿素激动剂 RQ-00538053 对雌性大鼠与雄性大鼠结直肠运动的影响。静脉给予 RQ-00538053 可增强雌性大鼠的结直肠运动。然而，需要大约十倍高的剂量才能诱导雌性大鼠产生类似于雄性大鼠的反应。即使将激动剂鞘内给予雌性大鼠的腰骶脊髓，也需要更高的剂量。RT-qPCR 的结果表明，雌性大鼠腰骶脊髓中胃饥饿素受体的表达水平低于雄性大鼠，这表明受体的低表达水平可能至少部分导致了 RQ-00538053 作用的性别差异。胃饥饿素激动剂的这种性别二态性作用对于未来将胃饥饿素激动剂用作改善便秘的新型药物的工作将是重要的。
