AVP-induced activation of MAP kinase in vascular smooth muscle cells is mediated through protein kinase C.
Arginine vasopressin (AVP) has been shown to stimulate tyrosine phosphorylation and activation of p42 mitogen-activated protein (MAP) kinase (p42MAPK) in vascular smooth muscle cells (VSMC). In VSMC, AVP increases free intracellular Ca2+ concentration ([Ca2+]i) and activates protein kinase C (PKC) through activation of phospholipase C. The contribution of PKC and [Ca2+]i in p42MAPK regulation was therefore determined. Activation of PKC by phorbol 12-myristate 13-acetate (PMA) stimulated tyrosine phosphorylation and activation of p42MAPK to the same extent as AVP. Inhibition of PKC by staurosporine or downregulation of PKC by PMA pretreatment abolished AVP-induced stimulation of p42MAPK. When [Ca2+]i was elevated to the same level as with AVP, using either ionomycin (0.1 microM) or thapsigargin (0.1 microM), MAP kinase was only partially activated. Elevation of [Ca2+]i to supraphysiological levels by 1 microM ionomycin stimulated MAP kinase activity to the same extent as AVP. This effect was blocked by downregulation of PKC. The intracellular Ca2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid] blocked AVP-induced [Ca2+]i increase but did not affect AVP stimulation of p42MAPK. Thus AVP-induced activation of p42MAPK requires only the activation of PKC but not an increase in [Ca2+]i.
Kribben
A
A
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Wieder
E D
ED
Li
X
X
van Putten
V
V
Granot
Y
Y
Schrier
R W
RW
Nemenoff
R A
RA
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D007425:Intracellular Membranes / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D009994:Osmolar Concentration; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D002118:Calcium