Effect of epinephrine on the regulation of Na+/H+ exchange in human platelets.
In the present study, we investigated whether stimulation of platelets by epinephrine affects the Na+/H+ exchanger, an antiport that regulates the cytosolic pH (pHi). Epinephrine alone failed to modulate Na+/H+ exchange, as reflected by a constant fluorescence of the pHi indicator BCECF. In contrast, epinephrine accelerated Na+/H+ exchange upon stimulation with a threshold concentration of platelet activating factor (PAF). The extra Na+/H+ exchange was not caused by a better binding of PAF to platelets and occurred also in the presence of indomethacin, excluding a role for cyclooxygenase products. Epinephrine failed to mobilize Ca2+i (measured by fura-2 fluorescence) and did not activate protein kinase C ([32P]pleckstrin) or phospholipase C ([32P]phosphatidic acid). In combination with PAF, epinephrine left the PAF-induced mobilization of Ca2+i and accumulation of [32P]phosphatidic acid unchanged, but induced a 1.3-fold increase in the phosphorylation of pleckstrin. These data indicate that epinephrine enhances Na+/H+ exchange via a direct effect of alpha 2A-adrenergic receptors on protein kinase C.
Nieuwland
R
R
Department of Haematology, University Hospital Utrecht, The Netherlands.
Siffert
W
W
Akkerman
J W
JW
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D002352:Carrier Proteins / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010972:Platelet Activating Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D012964:Sodium / Q000097:blood; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D010972:Platelet Activating Factor; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D011493:Protein Kinase C; D002118:Calcium; D004837:Epinephrine