Role of alpha-adrenergic mechanisms in kappa receptor mediated diuresis inrats

The effect of peripheral administration of selective kappa opioid agonists and morphine and the involvement of adrenergic mechanisms on the urinary ou tput in normally hydrated rats was studied. Selective kappa opioid agonists , U-50,488H and PD117302 significantly increased the urinary output and the y were found to be equipotent. Buprenorphine - a partial agonist - failed t o increase the urinary output per se (0.1 to 3 mg/kg, i.p.); and inhibited the urinary output induced by PD117302 (15mg/kg, i.p.) indicating that PD11 7302-induced urinary output is mediated through kappa-opioid receptors. Further, the influence of alpha-adrenoceptor antagonists, Phentolamine, Pra zosin and Yohimbine on kappa opioid agonist-induced diuresis was also studi ed. Go-administration of Phentolamine inhibited the PD117302 induced urinar y output. Prazosin (0.2-1 mg/kg, i.p.) also inhibited the PD117302 induced urinary output. However, its antagonistic effect did not persist beyond 4 h r. Yohimbine (5 mg/kg, i. p.) when administered with PD117302 resulted in a decrease in the urinary output induced by the agonist. Finally, pretreatme nt of the rats with reserpine decreased the urinary output induced by PD117 302 and U-50,488H. These studies demonstrate the extensive involvement of the endogenous catec holamine system and the alpha-adrenoceptors in the kappa opioid receptor me diated urinary output in normally hydrated rats.