Regulation of protein synthesis by alpha 1-adrenergic receptor subtypes in cultured rabbit aortic vascular smooth muscle cells.
To investigate the role of the sympathetic nervous system in maintenance and remodeling of vascular smooth muscle, we have examined regulation of protein synthesis by alpha 1-adrenergic receptors (alpha 1-AR) in cultured rabbit aortic vascular smooth muscle cells (VSMC). Stimulation of postconfluent cultures (passages 2-6) in serum-free growth medium with the alpha-AR agonist phenylephrine (PE, 30 microM) increases protein synthesis, measured as [3H]leucine incorporation into protein (146 +/- 5%, p < or = 0.001) and total protein content (117 +/- 2%, p < or = 0.001). PE treatment does not affect cellular proliferation or [3H]thymidine incorporation into DNA. PE-stimulated protein synthesis is evident within 24 h, sustained over 96 h, concentration-dependent, and saturable. PE-elicited responses are completely inhibited by the alpha 1-AR antagonist prazosin but not by the alpha 2-AR antagonist yohimbine or the beta-AR antagonists propranolol and atenolol; the beta-AR agonist isoproterenol is ineffective. Competition with [3H]prazosin occupancy of alpha 1-AR and agonist-elicited [3H]leucine incorporation by subtype-selective receptor antagonists (WB4101 and 5-methylurapidil, alpha 1A; chloroethylclonidine, alpha 1B) demonstrates that these cells express a majority of alpha 1B-AR (75%) relative to alpha 1A-AR (25%), which elicit protein metabolism in proportion to their relative abundances. These results indicate that alpha 1B-AR predominate in coupling to metabolic responses, in contrast to previous reports that contractile responses in this tissue are preferentially mediated by alpha 1A-AR.
Siwik
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DA
Department of Pharmacology, University of Illinois at Chicago 60612, USA.
Brown
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D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011817:Rabbits; D013997:Time Factors
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine