title: Regulation of renin secretion through reversible phosphorylation of myosin by myosin light chain kinase and protein phosphatase type 1.
abstract: Possible involvement of reversible phosphorylation and dephosphorylation of myosin light chain (MLC) by myosin light chain kinase (MLCK) and protein phosphatases (PPases), respectively, in the Ca++-calmodulin-dependent inhibition of renin secretion was investigated with the use of putative MLCK inhibitor ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine] and PPase type1 (PPase-1) and type 2A (PPase-2A) inhibitor calyculin A. ML-7 (1 x 10(-)6 to 3 x 10(-)5 M) increased renin secretion in vitro from rat renal cortical slices under "resting" conditions in a concentration-dependent manner with maximal 2.5-fold stimulation. Furthermore, Ca++-induced inhibition of renin secretion in depolarizing K+-rich Krebs-Ringer bicarbonate not only was prevented completely but also reversed by ML-7 in a concentration-dependent and reversible manner. On the other hand, calyculin A (3 x 10(-)6 M) blocked both effects of ML-7 on stimulation and reversal of renin secretion independently of intracellular Ca++ concentrations. Such antagonistic effects of ML-7 and calyculin A on renin secretion most likely resulted from their respective effects on the level of MLC phosphorylation: ML-7 stimulates renin secretion by decreasing phosphorylation of MLC through its inhibition of MLCK, whereas calyculin A inhibits secretion by increasing phosphorylation of MLC through its inhibition of PPase-1. By inference from these results, MLC may be the target protein involved in regulation of the renin secretory process by Ca++: Ca++-calmodulin phosphorylates MLC via activating MLCK and thereby inhibits renin secretion, whereas dephosphorylation of phosphorylated MLC by PPase-1 reverses the inhibited secretion. We therefore conclude that reversible phosphorylation of MLC may be an important biochemical step determining the rate of renin secretion from the juxtaglomerular cell.
authors.affiliation: Departments of Physiology and Pharmacology, University of Ulsan College of Medicine, and Asan Institute for Life Science, Seoul 138-040, Korea.
authors.forename: M H
authors.initials: MH
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: J W
authors.initials: JW
authors.lastname: Chang
authors.forename: Y S
authors.initials: YS
authors.lastname: Hong
authors.forename: H W
authors.initials: HW
authors.lastname: Kim
authors.forename: C S
authors.initials: CS
authors.lastname: Park
mesh_terms: D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D008387:Marine Toxins; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D009281:Naphthalenes; D010080:Oxazoles; C070571:ML 7; C059041:calyculin A; D009219:Myosin-Light-Chain Kinase; D010749:Phosphoprotein Phosphatases; D012083:Renin; D009218:Myosins; D011188:Potassium; D002118:Calcium