Caveolin-1 regulates contractility in differentiated vascular smooth muscle

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 alpha agonist. Peptide loading also resulted in a significant inhibition of phorbol ester- induced adducin Ser(662) phosphorylation, an intracellular monitor of PKC kinase activity, ERK1/ 2 activation, and Ser(789) phosphorylation of the actin binding protein caldesmon. alpha- 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 alpha- agonist were obtained with the cholesterol- depleting agent methyl- beta- 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.