Up-regulation of alpha1A-adrenoceptors in rat mesenteric artery involves intracellular signal pathways.
The aim of the present study was to investigate if there is an altered expression of alpha-adrenoceptors during organ culture of rat mesenteric artery segments by using a sensitive pharmacological method and molecular biological techniques. Noradrenalin (NA) induced contraction via alpha1-adrenoceptors. The contraction and alpha1A-adrenoceptor mRNA levels were elevated during organ culture. Transcriptional inhibitor actinomycin D, translational inhibitor cycloheximide, protein kinase C inhibitors (staurosporine and RO31-8220) and mitogen-activated protein kinase (MAPK) pathway inhibitors (SB386023, U0126 and SB239063) prevented the increase in NA-induced contractions. The amount of alpha1A-adrenoceptor mRNA was significantly lower in the artery segments cultured for 1 day in the presence of specific MAPK extracellular signal-regulated protein kinase1/2 pathway inhibitor SB386023 than that of the cultured controls. SB386023 did not affect alpha2-adrenoceptor mRNA level. Our results suggest that the up-regulation of alpha1A-adrenoceptors involves transcription and intracellular signal transduction via the protein kinase C and the ERK 1/2 pathways.
Cao
Yong-Xiao
YX
Division of Experimental Vascular Research, Institution of Medicine, Lund University, Sweden.
Xu
Cang-Bao
CB
Luo
Guo-Gang
GG
Edvinsson
Lars
L
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D017538:Mesenteric Artery, Superior; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D015854:Up-Regulation; D014661:Vasoconstriction / Q000502:physiology*
C547715:Adra1a protein, rat; D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011743:Pyrimidines; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D019311:Staurosporine; C406525:SB 239063; D009638:Norepinephrine