Cytosolic calcium as a second messenger for collagen-induced platelet responses.
We showed previously that direct platelet activation by collagen involves an increase in the platelet cytosolic free Ca2+ concentration ([Ca2+]i) but that this increase is not required for the adhesion of platelets to collagen. We now report that collagen-induced arachidonic acid liberation, myosin phosphorylation and 5-hydroxytryptamine secretion are dependent on increases in [Ca2+]i, as they were markedly inhibited in platelets loaded with the acetoxymethyl ester of the Ca2+ chelator BAPTA but not in cells loaded with the acetoxymethyl ester of the non-chelating diazo-3. BAPTA also partially inhibited the rate of collagen-induced phosphatidic acid (PtdA) formation but had little effect on increases in phosphorylation of pleckstrin (47 kDa protein; P47). From these results we infer that collagen-induced increases in [Ca2+]i are required for dense granule secretion and arachidonic acid liberation, but are not necessary for stimulation of the protein kinase C pathway.
Smith
J B
JB
Department of Pharmacology, Temple University Medical School, Philadelphia, PA 19140.
Selak
M A
MA
Dangelmaier
C
C
Daniel
J L
JL
D000345:Affinity Labels; D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000097:blood / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology*; D003600:Cytosol / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009218:Myosins / Q000378:metabolism; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects; D015290:Second Messenger Systems / Q000502:physiology*
D000345:Affinity Labels; D010712:Phosphatidic Acids; D004533:Egtazic Acid; D003094:Collagen; D009218:Myosins; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium