Dual control of the intracellular pH in aortic smooth muscle cells by a cAMP-sensitive HCO3-/Cl- antiporter and a protein kinase C-sensitive Na+/H+ antiporter.
Two mechanisms are involved in the regulation of the intracellular pH (pHi) of aortic smooth muscle cells: the Na+/H+ antiporter and a Na+-independent HCO3-/Cl- antiporter. The Na+/H+ antiporter acts as a cell alkalinizing mechanism. It is activated by vasopressin and by phorbol esters when cells are incubated in the presence of bicarbonate but is not affected in the absence of bicarbonate. The HCO3-/Cl- antiporter acts as a cell acidifying mechanism. Agents such as forskolin, 8-Br-cAMP, and isoproterenol which raise intracellular cAMP levels inhibit the HCO3-/Cl- antiporter by shifting its pHi dependence in the alkaline direction. Thus, within the same cell type, different hormones control pHi variations by acting on different pHi regulating systems. An increase in pHi can be achieved either by a stimulation of a cell alkalinizing mechanism or by inhibition of a cell acidifying mechanism. A change of the activity of one pHi regulating mechanism modifies the responsiveness of the other to regulatory agents. Bicarbonate turns on the HCO3-/Cl- antiporter, decreases pHi and allows its regulation by protein kinase C through the Na+/H+ antiporter. Inhibition of the HCO3-/Cl- antiporter by cAMP increases the pHi and switches off the protein kinase C-mediated regulation.
Vigne
P
P
Centre de Biochimie du Centre National de la Recherche Scientifique, Nice, France.
Breittmayer
J P
JP
Frelin
C
C
Lazdunski
M
M
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D008565:Membrane Proteins; D017923:Sodium-Hydrogen Exchangers; D001127:Arginine Vasopressin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012964:Sodium; D000242:Cyclic AMP; D011493:Protein Kinase C