Serotonin-induced protein kinase C activation in cultured rat heart endothelial cells

Authors
Citation
Hz. Lee et Ch. Wu, Serotonin-induced protein kinase C activation in cultured rat heart endothelial cells, EUR J PHARM, 403(3), 2000, pp. 195-202
Citations number
47
Categorie Soggetti
Pharmacology & Toxicology
Journal title
EUROPEAN JOURNAL OF PHARMACOLOGY
ISSN journal
00142999 → ACNP
Volume
403
Issue
3
Year of publication
2000
Pages
195 - 202
Database
ISI
SICI code
0014-2999(20000908)403:3<195:SPKCAI>2.0.ZU;2-2
Abstract
This study examined whether serotonin can activate protein kinase C in rat heart endothelial cells. Protein kinase C isozyme translocation was examine d by Western blot analysis with isozyme-specific anti-protein kinase C anti body. In this study, only alpha protein kinase C isozyme was found to be tr anslocated from the cytosolic to the particulate fractions after serotonin stimulation. The effect of serotonin on the incorporation of P-32 from [gam ma-P-32]ATP into peptide substrate was studied as another indicator of prot ein kinase C activation. The experiments in this study demonstrated that th e Ca2+-phospholipid-dependent protein kinase, protein kinase C, was activat ed by serotonin. By investigating [H-3]phorbol 12,13-dibutyrate binding to protein kinase C and trypsin-treated protein kinase C activity, we demonstr ated that the site of action of serotonin is probably the regulatory domain of protein kinase C. Finally, we also demonstrated that serotonin had no e ffect on the intracellular concentration of cyclic nucleotides (cAMP, cGMP) . These findings support the hypothesis that protein kinase C may be an imp ortant participant in serotonin-induced endothelial cell contraction and ba rrier dysfunction. (C) 2000 Elsevier Science B.V. All rights reserved.