ボンベシン3型受容体欠損マウスの膀胱・前立腺における自律神経受容体機能の変化

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  • Functional changes in the autonomic receptors distributed in smooth muscle of the urinary bladder and prostate of the bombesin receptor type 3 knockout mice

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Urinary symptoms such as urinary urgency and dysuria, which are commonly found in patients with prostatic hypertrophy, are also associated with the development of diabetes mellitus. Mice which lack the expression of bombesin type-3 receptors (BRS-3 deficient mice) are known to develop obesity, hypertension or hyperinsulinemia, similar to that seen in patients suffering from diabetes mellitus. Experiments were carried out to investigate the possible alteration of the mechanical properties of smooth muscle of the urinary bladder and prostate in response to stimulation of muscarinic and adrenergic receptors, in BRS-3 deficient mice, in comparison to the results obtained in similar preparations from wild type mice. In isolated smooth muscle preparations from the urinary bladder, the amplitude of contractions produced by carbachol and the relaxation induced by isoproterenol in preparations pre-constricted with carbachol were significantly larger in BRS-3 deficient mice compared to wild type mice, although there was no significant difference in the tension developed by high-potassium (high-K) solutions between BRS-3 deficient and wild type mice. In smooth muscle preparations isolated from the prostate, the amplitude of contraction produced by phenylephrine was not significantly different between BRS-3 deficit and wild type mice. Experiments using RT-PCR methods revealed that the expression of muscarinic M2 and M3 receptors in the urinary bladder tended to increase in BSR-3 deficient mice in comparison with wild type mice. These results suggested that urinary symptoms developed during diabetes mellitus may have a causal relation to the dysfunction of autonomic receptors distributed in smooth muscle of the urinary bladder but not in the prostate.

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