Regulation of Protein Synthesis by α1-Adrenergic Receptor Subtypes in Cultured Rabbit Aortic Vascular Smooth Muscle Cells

Publisher Website
Google Scholar
Abstract
Summary: 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 α1-adrenergic receptors (α1-AR) in cultured rabbit aortic vascular smooth muscle cells (VSMC). Stimulation of postconfluent cultures (passages 2-6) in serumfree growth medium with the α-AR agonist phenylephrine (PE, 30 μM) increases protein synthesis, measured as [3H]leucine incorporation into protein (146 ± 5%, p ≤ 0.001) and total protein content (117 ± 2%, p ≤ 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 α1-AR antagonist prazosin but not by the α2-AR antagonist yohimbine or the β-AR antagonists propranolol and atenolol; the β-AR agonist isoproterenol is ineffective. Competition with [3H]prazosin occupancy of α1-AR and agonist-elicited [3H]leucine incorporation by subtype-selective receptor antagonists (WB4101 and 5-methylurapidil, α1A; chloroethylclonidine, α1B) demonstrates that these cells express a majority of α1B-AR (75%) relative to α1A-AR (25%), which elicit protein metabolism in proportion to their relative abundances. These results indicate that α1B-AR predominate in coupling to metabolic responses, in contrast to previous reports that contractile responses in this tissue are preferentially mediated by α1A-AR.