Activation of sodium-proton exchange is not a prerequisite for Ca2+ mobilization and aggregation in human platelets.
Recently it has been suggested [(1987) Nature 325, 456-458; (1987) FEBS Lett. 212, 123-126] that the activation of Na+/H+ exchange is a prerequisite for platelet aggregation and the development of the Ca2+ signal. As direct evidence for the role of the Na+/H+-exchange pathway the inhibition of the Ca2+ signal by EIPA, a specific inhibitor of Na+/H+ exchange, was offered. Here we demonstrate that low concentrations of EIPA (below 1 microM) completely block Na+/H+ exchange while EIPA inhibits aggregation or Ca2+ mobilization only in concentrations 100-times greater than 1 microM. Moreover, another amiloride analogue, CBDMB, developed to act predominantly on Na+/Ca2+ exchange, does not affect Na+/H+ exchange in platelets but blocks aggregation and Ca2+ mobilization. We conclude that while Na+/H+ exchange has a fundamental role in platelet functions it is not prerequisite for the development of Ca2+ signal and aggregation.
Hunyady
L
L
Department of Physiology, Semmelweis University of Medicine, Budapest, Hungary.
Sarkadi
B
B
Cragoe
E J
EJ
Spät
A
A
Gárdos
G
G
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D011522:Protons; D012964:Sodium / Q000097:blood*; D017923:Sodium-Hydrogen Exchangers; D013917:Thrombin / Q000494:pharmacology
D002352:Carrier Proteins; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; C054391:5-(N-4-chlorobenzyl)-N-(2',4'-dimethyl)benzamil; D000584:Amiloride; D012964:Sodium; D013917:Thrombin; D002118:Calcium; C039614:ethylisopropylamiloride