Role of mitogen-activated protein kinases in endothelin ETB receptor up-regulation after organ culture of rat mesenteric artery.
Organ culture of isolated arteries results in increased levels of endothelin ET(B) (ET(B)) receptor mRNA and in enhanced ET(B) receptor mediated contraction. The present study was designed to pinpoint the mitogen-activated protein kinase (MAPK) subtype involved in up-regulation of ET(B) receptors after organ culture of rat mesenteric arteries. Western blot and selective antibodies towards constitutional and phosphorylated MAPKs revealed the appearance of phosphorylated MAPK of the extracellular signal-regulated kinases (ERK) 1/2 type at 3 h of organ culture. The functional ET(B) receptor and its mRNA expression were up-regulated after 24 h of organ culture. Following incubation with the MEK 1/2 specific inhibitor SB408039 or the raf inhibitor SB386023b the up-regulation was attenuated both for ET(B) receptor responses and in ET(B) receptor mRNA expression in the vessel segments. Neither Western blot nor myograph or mRNA analysis showed involvement of the other MAPKs studied. Our results suggest that the ERK1/2 MAPKs are involved in the endothelin ET(B) receptor up-regulation following organ culture.
Uddman
Erik
E
Division of Experimental Vascular Research, Department of Internal Medicine, Lund University Hospital, Wallenberg Neurocentrum, BMC A13 Solvegatan 17, SE-221 85 Lund, Sweden. Erik.Uddman@med.lu.se
Henriksson
Marie
M
Eskesen
Karen
K
Edvinsson
Lars
L
D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D011921:Rats, Inbred WKY; D044023:Receptor, Endothelin B / Q000096:biosynthesis*; D015854:Up-Regulation / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D044023:Receptor, Endothelin B; D020928:Mitogen-Activated Protein Kinases