Angiotensin II stimulation of Na-H antiporter activity is cAMP independent in OKP cells

A. Cano, R. T. Miller, R. J. Alpern, P. A. Preisig

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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 (J(Na-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 J(Na-H) in a concentration-dependent manner similar to the proximal tubule, with angiotensin II concentrations < 10-8 M stimulating and > 10-8 M inhibiting J(Na-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 J(Na- 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 J(Na-H) in OKP cells via a cAMP-independent mechanism mediated by an AT1 receptor and a pertussis toxin-sensitive G protein.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume266
Issue number6 35-6
StatePublished - 1994

Fingerprint

Sodium-Hydrogen Antiporter
Angiotensin II
Pertussis Toxin
GTP-Binding Proteins
8-Bromo Cyclic Adenosine Monophosphate
Opossums
1-Methyl-3-isobutylxanthine
Angiotensin Type 1 Receptor
Angiotensin Receptors
Losartan
Colforsin
Adenylyl Cyclases
Cyclic AMP
Dopamine
Cells
Kidney
Cell Line
Membranes

Keywords

  • AT receptor
  • cell pH
  • G protein
  • proximal tubule

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Angiotensin II stimulation of Na-H antiporter activity is cAMP independent in OKP cells. / Cano, A.; Miller, R. T.; Alpern, R. J.; Preisig, P. A.

In: American Journal of Physiology - Cell Physiology, Vol. 266, No. 6 35-6, 1994.

Research output: Contribution to journalArticle

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abstract = "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 (J(Na-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 J(Na-H) in a concentration-dependent manner similar to the proximal tubule, with angiotensin II concentrations < 10-8 M stimulating and > 10-8 M inhibiting J(Na-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 J(Na- 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 J(Na-H) in OKP cells via a cAMP-independent mechanism mediated by an AT1 receptor and a pertussis toxin-sensitive G protein.",
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