Interrelationship between growth factor-induced activation of the Na+/H(+)-antiporter and mobilization of intracellular Ca2+ in NIH3T3-fibroblasts.
Addition of serum growth factors or bombesin to quiescent NIH3T3-fibroblasts leads to a simultaneous mobilization of intracellular Ca2+ and an increase in cytosolic pH which is inhibitable by dimethylamiloride. The mobilization of intracellular Ca2+ is a pH-dependent process with an optimum at pH 7.1. In quiescent cells with a pHi greater than or equal to 6.8, inhibition of the Na+/H(+)-antiporter by dimethylamiloride or reduction of extracellular Na+ attenuates the growth factor induced Ca2(+)-response. It is concluded that the growth factor induced activation of the Na+/H(+)-antiporter facilitates the mobilization of Ca2+ by shifting the internal pH towards the optimum for the Ca2(+)-release.
Maly
K
K
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Hochleitner
B W
BW
Grunicke
H
H
D000584:Amiloride / Q000031:analogs & derivatives; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051379:Mice; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D006133:Growth Substances; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride; D001839:Bombesin; D002118:Calcium