Inhibitors of tyrosine phosphatases block angiotensin II inhibition of Na(+) pump.
To determine how angiotensin II inhibits the Na(+) pump (Na(+), K(+)-ATPase) in rat zona glomerulosa, we selectively blocked signaling proteins that could be activated by the angiotensin AT(1) receptor and known to affect Na(+) pump activity. Inhibitors of protein kinase C [calphostin C (1 microM); staurosporine (1 microM)], phospholipase A(2) [arachidonyl triflouromethyl ketone (25 microM); quinacrine (75 microM)], diacylgycerol lipase [RHC-80267 (5 microM)], and tyrosine phosphorylation [tyrphostin 47 (100 microM)] had no effect on angiotensin II inhibition of the Na(+) pump. On the other hand, inhibitors of tyrosine phosphatases [phenylarsine oxide (5 microM) and 4-bromotetramisole oxalate (100 microM)] blocked angiotensin II inhibition, where as inhibitors of serine/threonine phosphatases [okadaic acid (1 microM) and microcystin (1.5 microM)] did not. Thus, angiotensin II inhibition of the Na(+) pump may in part be mediated by a tyrosine phosphatase.
Yingst
D R
DR
Department of Physiology, Wayne State University School of Medicine, 540 E. Canfield Avenue, Detroit, MI 48201-1928, USA. dyingst@med.wayne.edu
Davis
J
J
Schiebinger
R
R
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001152:Arsenicals / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D009281:Naphthalenes / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013773:Tetramisole / Q000031:analogs & derivatives* / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
D001152:Arsenicals; D004791:Enzyme Inhibitors; D009281:Naphthalenes; C029341:oxophenylarsine; D000804:Angiotensin II; D016718:Arachidonic Acid; D014443:Tyrosine; C006226:4-bromotetramisole; D013773:Tetramisole; D011493:Protein Kinase C; D010741:Phospholipases A; D017027:Protein Tyrosine Phosphatases; D000254:Sodium-Potassium-Exchanging ATPase; D019311:Staurosporine; C058819:calphostin C