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Caveolin-1 regulates contractility in differentiated vascular smooth muscle

¹Boston Biomedical Research Institute, Watertown 02472; ²Department of Physiology, Tufts University Graduate School of Biomedical Sciences, Boston 02111; and ³Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Submitted 22 May 2003 ; accepted in final form 4 September 2003

Caveolin is a principal component of caveolar membranes. In the present study, we utilized a decoy peptide approach to define the degree of involvement of caveolin in PKC-dependent regulation of contractility of differentiated vascular smooth muscle. The primary isoform of caveolin in ferret aorta vascular smooth muscle is caveolin-1. Chemical loading of contractile vascular smooth muscle tissue with a synthetic caveolin-1 scaffolding domain peptide inhibited PKC-dependent increases in contractility induced by a phorbol ester or an agonist. Peptide loading also resulted in a significant inhibition of phorbol ester-induced adducin Ser⁶⁶² phosphorylation, an intracellular monitor of PKC kinase activity, ERK1/2 activation, and Ser⁷⁸⁹ phosphorylation of the actin binding protein caldesmon. -Agonist-induced ERK1–1/2 activation was also inhibited by the caveolin-1 peptide. Scrambled peptide-loaded tissues or sham-loaded tissues were unaffected with respect to both contractility and signaling. Depolarization-induced activation of contraction was not affected by caveolin peptide loading. Similar results with respect to contractility and ERK1/2 activation during exposure to the phorbol ester or the -agonist were obtained with the cholesterol-depleting agent methyl--cyclodextrin. These results are consistent with a role for caveolin-1 in the coordination of signaling leading to the regulation of contractility of smooth muscle.

signal transduction; extracellular signal-regulated kinase 1/2; caldesmon; decoy peptide