title: Regulation of protein synthesis by alpha 1-adrenergic receptor subtypes in cultured rabbit aortic vascular smooth muscle cells.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Illinois at Chicago 60612, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Siwik
authors.forename: R D
authors.initials: RD
authors.lastname: Brown
mesh_terms: 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
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine