Caveolin scaffolding peptide-1 interferes with norepinephrine-induced PLC-beta activation in cultured rat vascular smooth muscle cells.
Caveolins are a family of integral membrane proteins implicated in various cell functions, including the organization and inactivation of signaling molecules of G protein-coupled receptors. We tested the ability of human caveolin scaffolding peptide-1 (CSP-1) to regulate norepinephrine- (NE) or histamine (HIS)-induced increases on intracellular calcium concentrations ([Ca(2+)]i). In cultured rat vascular smooth muscle cells (VSMC), CSP-1 inhibited in a concentration-dependent manner NE- and HIS-induced increases in [Ca(2+)]i. This effect can be explained by the fact that CSP-1 inhibited a common signaling pathway. We tested the ability of this peptide to decrease the activation of PLC-beta3 and MAPK. CSP-1 inhibited the expression of the activated form of both enzymes, suggesting a direct effect of the peptide on the signaling cascade. CSP-1 readily enters VSMC in culture, as observed when FITC-conjugated CPS-1 is added to cell culture media. Taken together, these data suggest that CSP-1 blocks the effects of NE and HIS on [Ca(2+)]i of VSMC by inhibiting the activation of PLC-beta3 and MAPK.
Ocharan
Esther
E
Departamento de Posgrado e Investigacion, Escuela Superior de Medicina, Instituto Politécnico Nacional, México 11340, Mexico.
Asbun
Juan
J
Calzada
Claudia
C
Mendez
Enrique
E
Nuñez
Marisol
M
Medina
Roberto
R
Suarez
Gabriela
G
Meaney
Eduardo
E
Ceballos
Guillermo
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D051242:Caveolin 1 / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D054799:Phospholipase C beta; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism*
C495540:CAV1 protein, human; D051242:Caveolin 1; D007527:Isoenzymes; D006632:Histamine; D020929:Mitogen-Activated Protein Kinase Kinases; D010738:Type C Phospholipases; C518039:PLCB3 protein, human; D054799:Phospholipase C beta; C518041:Plcb3 protein, rat; D016650:Fluorescein-5-isothiocyanate; D002118:Calcium; D009638:Norepinephrine