Angiotensin II stimulation of Na-H antiporter activity is cAMP independent in OKP cells.
Angiotensin II has been reported to stimulate the proximal tubule Na-H antiporter by inhibition of adenylyl cyclase, and possibly by an adenosine 3',5'-cyclic monophosphate (cAMP)-independent mechanism. We examined the effect of angiotensin II on Na-H antiporter activity (JNa-H) in opossum kidney (OKP) cells, a proximal tubule-like cell line, whose Na-H antiporter resembles that of the proximal tubule apical membrane. We found that angiotensin II regulates JNa-H in a concentration-dependent manner similar to the proximal tubule, with angiotensin II concentrations < 10(-8) M stimulating and > 10(-8) M inhibiting JNa-H. The stimulatory effect of angiotensin II was blocked by 10(-8) M losartan and was pertussis toxin sensitive, suggesting mediation through an angiotensin II (AT1) receptor coupled to a pertussis toxin-sensitive G protein. Acute treatment with 10(-4) M 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) inhibited JNa-H by 30% and blocked angiotensin II-induced stimulation. However, angiotensin II (10(-12)-10(-6) M) did not inhibit basal, dopamine-stimulated, or forskolin-stimulated cAMP production measured in the presence of 3-isobutyl-1-methylxanthine (IBMX). In addition, angiotensin II had no effect on cAMP levels measured in the absence of IBMX. We conclude that angiotensin II at physiological concentrations stimulates JNa-H in OKP cells via a cAMP-independent mechanism mediated by an AT1 receptor and a pertussis toxin-sensitive G protein.
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8856.
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Cano
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Miller
R J
RJ
Alpern
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Preisig
D037361:Adenylate Cyclase Toxin; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D019808:Losartan; D009893:Opossums; D037342:Pertussis Toxin; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D001713:Biphenyl Compounds; D007093:Imidazoles; D017923:Sodium-Hydrogen Exchangers; D013777:Tetrazoles; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019808:Losartan