Inhibitors of tyrosine phosphatases block angiotensin II inhibition of Na + pump

• Published in: European journal of pharmacology 2000-10, Vol.406 (1), p.49-52
• Main Authors: Yingst, Douglas R., Davis, Joanne, Schiebinger, Rick
• Format: Article
• Language: English
• Subjects: Aldosterone; Angiotensin II - pharmacology; Animals; Arachidonic Acid - metabolism; Arsenicals - pharmacology; Biological and medical sciences; Ca 2; Endocrine kidney. Renin-angiotensin-aldosterone system; Enzyme Inhibitors - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Na; Na(+)–K(+)–exchanging ATPase; Naphthalenes - pharmacology; Ouabain; Phospholipases A - antagonists & inhibitors; Phospholipases A - metabolism; Phosphorylation - drug effects; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Protein Tyrosine Phosphatases - antagonists & inhibitors; Protein Tyrosine Phosphatases - metabolism; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors; Sodium-Potassium-Exchanging ATPase - metabolism; Staurosporine - pharmacology; Tetramisole - analogs & derivatives; Tetramisole - pharmacology; Tyrosine - metabolism; Vertebrates: endocrinology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00664-6

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 μM); staurosporine (1 μM)], phospholipase A 2 [arachidonyl triflouromethyl ketone (25 μM); quinacrine (75 μM)], diacylgycerol lipase [RHC-80267 (5 μM)], and tyrosine phosphorylation [tyrphostin 47 (100 μM)] had no effect on angiotensin II inhibition of the Na + pump. On the other hand, inhibitors of tyrosine phosphatases [phenylarsine oxide (5 μM) and 4-bromotetramisole oxalate (100 μM)] blocked angiotensin II inhibition, where as inhibitors of serine/threonine phosphatases [okadaic acid (1 μM) and microcystin (1.5 μM)] did not. Thus, angiotensin II inhibition of the Na + pump may in part be mediated by a tyrosine phosphatase.