Role of PKCa and PKC? in phenylephrine-induced contraction of rat corpora cavernosa.

Constriction of the penile vasculature prevents erection and is largely mediated by physiological agonists. We hypothesized that protein kinase C (PKC) may act as a regulator of penile vascular tone. Studies were designed to identify PKC isoforms present and to investigate their roles in phenylephrine-induced muscle contraction in the isolated rat corpora cavernosa. We demonstrated the presence of PKCa, ß, ?, ?, d, ?, and ? in rat corpora cavernosa and a subcellular distribution, which favored a membrane association for PKCa, ß, d, and ?. Phenylephrine (3?µM) generated an active stress of 9.6±1.5?mN/mm2 and was associated with a significant increase of PKCa and PKC? immunoreactivity in the particulate fraction. The amount of PKCa and PKC? in the particulate fraction rose by 36±4.4 and 51±2.2% with phenylephrine stimulation. Furthermore, the phenylephrine concentration-response curve was potentiated in the presence of phorbol 12-myristate13-acetate (PMA) (0.1?µM), a PKC activator (EC50: phenylephrine 1.0±0.8?µM vs phenylephrine+PMA 0.3±0.1?µM) and inhibited in the presence of chelerythrine chloride (30?µM), a PKC inhibitor (EC50: phenylephrine 1.0±0.8?µM vs phenylephrine+chelerythrine chloride 5.7±2.4?µM). Based on these results, we suggest a potential role for PKCa and PKC? in phenylephrine-induced smooth muscle tone of the rat cavernosum.International Journal of Impotence Research (2004) 16, 325-333. doi:10.1038/sj.ijir.3901164 Published online 27 November 2003 [ABSTRACT FROM AUTHOR]