ALPHA-1-ADRENERGIC RECEPTOR MESSENGER-RNA LEVEL IS REGULATED BY NOREPINEPHRINE IN RABBIT AORTIC SMOOTH-MUSCLE CELLS

Prolonged agonist exposure results in a decrease in the density of α1-adrenergic receptors in rabbit aortic smooth muscle cells. A cDNA for the α1-adrenergic receptor was used to assess the effect of norepinephrine on α1-adrenergic receptor mRNA level in cultured vascular smooth muscle cells from the rabbit aorta. Norepinephrine caused a transient decrease (81% ± 5% ; n = 9) in α1-adrenergic receptor mRNA. The effect was concentration dependent (EC50, ≈0.3 μM; maximal effect, 10 μM). 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 α1-adrenergic receptor and suggest that it involves one or more α1-adrenergic-coupled second messenger pathways. The decrease in α1-adrenergic receptor mRNA caused by norepinephrine exceeds that caused by actinomycin D, suggesting that norepinephrine may cause a decrease in the stability of α1-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 α1-adrenergic receptor mRNA level.