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. Superfusion of sliced cortex isolated from rat kidney with an isotonic solution containing more than 20 mM of KCl significantly stimulated the release of kallikrein. The latter in vitro result supported another mechanism for the release of renal kallikrein from kidney other than biosynthesis of kallikrein by 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'-cyclohexylhydr ochloride (U37883A), and barium chloride, which inhibit an efflux of intracellular potassium to block the channel, showed a significant increase of the kallikrein release from the slice of kidney cortex. Cytochalasin B, which inhibits a polymerization of actin, also showed a stimulation of the release. Enhanced release of kallikrein by a high potassium or ATP-sensitive potassium channel blocker was reduced by the absence of calcium ion and the presence of voltage-dependent calcium channel blocker in the superfused solution. These results indicate the ATP-sensitive potassium channel which couples to voltage-dependent calcium channel and cytoskeletal protein could be involved in a rapid secretory mechanism of renal kallikrein by high potassium.
Hayashi
I
I
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. hayashii@med.kitasato-u.ac.jp
Fujita
T
T
Majima
M
M
Katori
M
M
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002414:Cations, Monovalent; D004305:Dose-Response Relationship, Drug; D054086:KATP Channels; D007610:Kallikreins / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley
D018528:ATP-Binding Cassette Transporters; D002414:Cations, Monovalent; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D007610:Kallikreins; D011188:Potassium