Kappa Opioid Agonist-Induced Diuresis: Characteristics, Mechanisms, and Beyond

Activation of the kappa opioid receptor (KOR) induces antinociception, anti-pruritic activity, diuresis, sedation, and dysphoria. KOR agonist-induced diuresis is characterized as water diuresis, in which water excretion with urine is increased without altering electrolyte excretion. Both centrally and peripherally acting KOR agonists promote diuresis. KOR antagonists block KOR agonist-evoked diuresis suggesting that the diuretic effect is through activation of the KOR. Studies in different experimental animal species and in humans indicate that KOR agonists decrease antidiuretic hormone (ADH) secretion and release from the hypothalamus and posterior pituitary; decrease response to ADH in kidneys; increase renal sympathetic nerve activity; and increase adrenaline, noradrenaline, and dopamine release from the adrenal medulla. The therapeutic potentials of KOR agonists as water diuretics have been studied in animal models of cerebral edema due to ischemia and intracranial mass, hypertension, and cirrhosis. This chapter reviews characteristics, possible mechanisms, as well as therapeutic potentials of KOR agonist-induced diuresis.