Role of PKCalpha and PKCiota in phenylephrine-induced contraction of rat corpora cavernosa.

Abstract

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 PKCalpha, beta, gamma, epsilon, delta, eta, and iota in rat corpora cavernosa and a subcellular distribution, which favored a membrane association for PKCalpha, beta, delta, and iota. Phenylephrine (3 microM) generated an active stress of 9.6 +/- 1.5 mN/mm2 and was associated with a significant increase of PKCalpha and PKCiota immunoreactivity in the particulate fraction. The amount of PKCalpha and PKCiota 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 microM), a PKC activator (EC50: phenylephrine 1.0 +/- 0.8 microM vs phenylephrine + PMA 0.3 +/- 0.1 microM) and inhibited in the presence of chelerythrine chloride (30 microM), a PKC inhibitor (EC50: phenylephrine 1.0 +/- 0.8 microM vs phenylephrine + chelerythrine chloride 5.7 +/- 2.4 microM). Based on these results, we suggest a potential role for PKCalpha and PKCiota in phenylephrine-induced smooth muscle tone of the rat cavernosum.