A secretory mechanism of renal kallikrein by a high potassium ion; a possible involvement of ATP-sensitive potassium channel

A relatively rapid excretion of urinary kallikrein into urine was observed by an intravenous infusion of high potassium in anesthetized rats. Superfus ion of sliced cortex isolated from rat kidney with an isotonic solution con taining more than 20 mM of KCl significantly stimulated the release of kall ikrein. The latter in vitro result supported another mechanism for the rele ase of renal kallikrein from kidney other than biosynthesis of kallikrein b y aldosterone released from adrenal cortex after loading of high potassium and the mechanism was elucidated. ATP-sensitive potassium channel blockers, glibenclamide, 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydroc hloride (U37883A), and barium chloride, which inhibit an efflux of intracel lular potassium to block the channel, showed a significant increase of the kallikrein release from the slice of kidney cortex. Cytochalasin B, which i nhibits a polymerization of actin, also showed a stimulation of the release . Enhanced release of kallikrein by a high potassium or ATP-sensitive potas sium channel blocker was reduced by the absence of calcium ion and the pres ence of voltage-dependent calcium channel blocker in the superfused solutio n. These results indicate the ATP-sensitive potassium channel which couples to voltage-dependent calcium channel and cytoskeletal protein could be inv olved in a rapid secretory mechanism of renal kallikrein by high potassium. (C) 1999 Elsevier Science B.V. All rights reserved.