Defective leukocyte adenylate cyclase function in hypokalemia

Abstract

Patients with hypokalemia due to Bartter's syndrome show an increase in adrenergic nervous system function with significantly elevated plasma norepinephrine excretion. Prolonged exposure to neurotransmitters or hormones is known to lead to a down-regulation of target-cell responsiveness. We measured cyclic AMP generation by leukocytes in response to the beta-adrenergic agonist isoproterenol and to prostaglandin E1 (PGE1) in six patients with Bartter's syndrome. As compared to normal controls, the response of cyclic AMP production by leukocytes to stimulation by 1-isoproterenol or PGE1 was significantly decreased. These results indicate that in Bartter's syndrome and probably in other diseases involving hypokalemia isoproterenol- and PGE1-sensitive adenylate cyclase activities of leukocytes are reduced. Because the effect of PGE1 on adenylate cyclase is not mediated through the specific beta-adrenoceptor, it is possible that a defect in receptor-adenylate cyclase coupling or a more distal post-receptor defect is responsible for the reduction in cyclic AMP production.