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

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 requi...

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Bibliographic Details
Published in:The journal of physiological sciences 2024-11, Vol.74 (1), p.54, Article 54
Main Authors: Tsukamoto, Shumpei, Sawamura, Tomoya, Yuki, Natsufu, Horii, Kazuhiro, Horii, Yuuki, Homma, Takeshi, Saito, Shouichiro, Shiina, Takahiko, Shimizu, Yasutake
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Language:English
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Summary: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.
ISSN:1880-6562
1880-6546
1880-6562
DOI:10.1186/s12576-024-00949-w