Alpha 1-adrenergic receptor mRNA level is regulated by norepinephrine in rabbit aortic smooth muscle cells.
Prolonged agonist exposure results in a decrease in the density of alpha 1-adrenergic receptors in rabbit aortic smooth muscle cells. A cDNA for the alpha 1-adrenergic receptor was used to assess the effect of norepinephrine on alpha 1-adrenergic receptor mRNA level in cultured vascular smooth muscle cells from the rabbit aorta. Norepinephrine caused a transient decrease (81% +/- 5%; n = 9) in alpha 1-adrenergic receptor mRNA. The effect was concentration dependent (EC50, approximately 0.3 microM; maximal effect, 10 microM). The maximum decrease occurred after 4 hr of exposure to norepinephrine and was followed by a gradual return to control levels by 24 hr. The decrease in mRNA level was blocked by prazosin, but not propranolol, and was mimicked by phenylephrine. These results indicate that the effect is mediated by stimulation of the alpha 1-adrenergic receptor and suggest that it involves one or more alpha 1-adrenergic-coupled second messenger pathways. The decrease in alpha 1-adrenergic receptor mRNA caused by norepinephrine exceeds that caused by actinomycin D, suggesting that norepinephrine may cause a decrease in the stability of alpha 1-adrenergic receptor mRNA. Actinomycin D also blocked the norepinephrine-induced decrease in mRNA level, further suggesting that the effect of norepinephrine requires induction of transcription, presumably leading to synthesis of a labile factor that is necessary for the effect of norepinephrine on alpha 1-adrenergic receptor mRNA level.
Izzo
N J
NJ
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Seidman
C E
CE
Collins
S
S
Colucci
W S
WS
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D015342:DNA Probes; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000235:genetics*
D015342:DNA Probes; D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D003609:Dactinomycin; D009638:Norepinephrine