Regulation of renin secretion through reversible phosphorylation of myosin by myosin light chain kinase and protein phosphatase type 1.

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.

• Publication year

  1998

• Venue

  Journal of Pharmacology and Experimental Therapeutics

• Publication date

  1998-06-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/s0022-3565(24)37539-1PMID 9618396
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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