title: AVP-induced activation of MAP kinase in vascular smooth muscle cells is mediated through protein kinase C.
abstract: 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.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Denver 80262.
authors.forename: A
authors.initials: A
authors.lastname: Kribben
authors.forename: E D
authors.initials: ED
authors.lastname: Wieder
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: V
authors.initials: V
authors.lastname: van Putten
authors.forename: Y
authors.initials: Y
authors.lastname: Granot
authors.forename: R W
authors.initials: RW
authors.lastname: Schrier
authors.forename: R A
authors.initials: RA
authors.lastname: Nemenoff
mesh_terms: 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
chemical_list: 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