Sexual dimorphism in prokinetic effects of a ghrelin agonist acting through the lumbosacral defecation center in rats.

IF 2.6 4区医学 Q2 PHYSIOLOGY Journal of Physiological Sciences Pub Date : 2024-11-22 DOI:10.1186/s12576-024-00949-w

Shumpei Tsukamoto, Tomoya Sawamura, Natsufu Yuki, Kazuhiro Horii, Yuuki Horii, Takeshi Homma, Shouichiro Saito, Takahiko Shiina, Yasutake Shimizu

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Abstract

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.

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通过腰骶部排便中枢作用的胃泌素激动剂对大鼠促排便作用的性别双态性。

我们研究了中枢渗透性胃泌素激动剂 RQ-00538053 对雌性大鼠结肠直肠运动的影响。静脉注射 RQ-00538053 可增强雌性大鼠的结肠直肠运动能力。然而，要诱导雌性大鼠产生与雄性大鼠相似的反应，需要高出约十倍的剂量。即使在雌性大鼠腰骶部脊髓内注射该激动剂，也需要更高的剂量。RT-qPCR 的结果显示，雌性大鼠腰骶脊髓中胃泌素受体的表达水平低于雄性大鼠，这表明受体表达水平较低可能至少部分导致了 RQ-00538053 作用的性别差异。胃泌素受体激动剂的性别差异作用对今后旨在利用胃泌素受体激动剂作为新型药物改善便秘的工作具有重要意义。

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来源期刊

Journal of Physiological Sciences 医学-生理学

CiteScore

4.40

自引率

4.30%

发文量

审稿时长

6-12 weeks

期刊介绍： The Journal of Physiological Sciences publishes peer-reviewed original papers, reviews, short communications, technical notes, and letters to the editor, based on the principles and theories of modern physiology and addressed to the international scientific community. All fields of physiology are covered, encompassing molecular, cellular and systems physiology. The emphasis is on human and vertebrate physiology, but comparative papers are also considered. The process of obtaining results must be ethically sound. Fields covered: Adaptation and environment Autonomic nervous function Biophysics Cell sensors and signaling Central nervous system and brain sciences Endocrinology and metabolism Excitable membranes and neural cell physiology Exercise physiology Gastrointestinal and kidney physiology Heart and circulatory physiology Molecular and cellular physiology Muscle physiology Physiome/systems biology Respiration physiology Senses.