MP11-12\u2003GHRELIN-MEDIATED REGULATION OF THE MICTURITION REFLEX IN URETHANE-ANESTHETIZED RATS

Abstract

INTRODUCTION AND OBJECTIVES: Ghrelin, a 28 amino acid growth hormone, is widely distributed throughout the peripheral and central nervous systems. Ghrelin′s many physiological functions include growth promotion, suppression of inflammation, and enhancement of food intake. Increasingly, evidence suggests an antinociceptive role of ghrelin in murine pain models. However, whether ghrelin also plays a role in controlling the micturition reflex is unclear. Therefore, we investigated the effects of intravenous administration of ghrelin on the micturition reflex in rats. METHODS: Continuous cystometrograms (CMG, 0.04 ml/min) were performed in female Sprague-Dawley rats (228-252 g) under urethane anesthesia. Stable micturition cycles were established, and ghrelin was then administered intravenously to evaluate changes in bladder activity. In experiments examining the role of opioid systems, ghrelin was administered intravenously when the first bladder contraction was observed after intravenous administration of naloxone methiodide, an opioid receptor antagonist. Cystometric parameters were recorded and compared before and after drug administration. RESULTS: Intravenous administration of ghrelin at 300, 600, and 900 µg/kg (n=6 per dose) increased intercontraction intervals in a dose-dependent fashion to 119.1 ± 3.8%, 147.5 ± 8.3%, and 154.4 ± 11.5% of the control value, respectively (p <0.01). These inhibitory effects were seen immediately after administration and returned to the pre-control level within 80 minutes. Intravenous administration of ghrelin at 300, 600, and 900 µg/kg (n=6 per dose) also increased threshold pressure in a dose-dependent fashion to 9.58 ± 1.03 cmH2O, 12.7 ± 1.51 cmH2O, and 15.6 ± 3.11 cmH2O, respectively (p <0.01). There were no significant changes in baseline pressure or residual urine at any doses tested. These inhibitory effects of ghrelin (900 µg/kg, n=6) were antagonized by intravenous administration of naloxone methiodide (3 mg/kg, n=6). CONCLUSIONS: These results indicate that in urethane-anesthetized rats, ghrelin inhibits the micturition reflex through the opioid mechanism. Thus, ghrelin could be effective for the treatment of bladder dysfunction, such as overactive bladder. Source of Funding: None