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Role of PKCα and PKCι in phenylephrine-induced contraction of rat corpora cavernosa

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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 PKCα, β, γ, ɛ, δ, η, and ι in rat corpora cavernosa and a subcellular distribution, which favored a membrane association for PKCα, β, δ, and ι. Phenylephrine (3 μM) generated an active stress of 9.6±1.5 mN/mm2 and was associated with a significant increase of PKCα and PKCι immunoreactivity in the particulate fraction. The amount of PKCα and PKCι 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 PKCα and PKCι in phenylephrine-induced smooth muscle tone of the rat cavernosum.

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Acknowledgements

This work was supported by National Institute of Health (NIH DK59467) grant awarded to CJ Wingard. The authors are grateful to Dr John A Johnson for fruitful discussions during these studies.

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Husain, S., Young, D. & Wingard, C. Role of PKCα and PKCι in phenylephrine-induced contraction of rat corpora cavernosa. Int J Impot Res 16, 325–333 (2004). https://doi.org/10.1038/sj.ijir.3901164

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