Effect of concanavalin A on serotonin transport into blood platelets: possible involvement of protein kinase C.
Possible involvement of protein kinases in the serotonin (5-HT) transport system in platelets and the inhibitory effect of concanavalin A (Con A) on platelet 5-HT uptake were investigated. Staurosporine and K-252a, highly active inhibitors of protein kinases, did not inhibit 5-HT transport, but they antagonized the inhibitory effect of Con A on 5-HT uptake. KT5720, a protein kinase A inhibitor that has no effect on protein kinase C, neither affected 5-HT transport nor antagonized the inhibitory effect of Con A on 5-HT uptake. The Con A effect on 5-HT uptake was also antagonized by LaCl3, a Ca++ entry blocker. When the activity of Ca++ transport into platelets was estimated, Con A was shown to have a stimulative effect, which was antagonized by alpha-methyl-D-mannoside, a specific antagonist of Con A binding to cell membrane glycoproteins. Furthermore, Con A was shown to stimulate the protein kinase C activity of platelets, which phosphorylates a 40-kDa platelet protein; the Con A effects were antagonized by alpha-methyl-D-mannoside, staurosporine and K-252a, but not by KT5720. We suggest that the activation of protein kinase C and phosphorylation of 40-kDa protein might be involved in the inhibitory effect of Con A on platelet 5-HT transport.
Jikoh
Y
Y
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Nishio
H
H
Okugawa
K
K
Segawa
T
T
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002132:Calcium Radioisotopes; D002227:Carbazoles / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology*; D066298:In Vitro Techniques; D026121:Indole Alkaloids; D007211:Indoles / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000097:blood; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000097:blood*; D019311:Staurosporine
D000470:Alkaloids; D001798:Blood Proteins; D002132:Calcium Radioisotopes; D002227:Carbazoles; D026121:Indole Alkaloids; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C028521:lanthanum chloride; D003208:Concanavalin A; D012701:Serotonin; C057416:KT 5720; D007811:Lanthanum; C049985:staurosporine aglycone; D011494:Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium