Comparison of the involvement of protein kinase C in agonist-induced contractions in mouse aorta and corpus cavernosum

Liming Jin, Cleber E. Teixeira, R Clinton Webb, Romulo Leite

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Protein kinase C (PKC) is involved in the regulation of vascular smooth muscle contraction. However, the role of PKC in erectile function is poorly understood. This study investigated whether PKC mediates agonist-induced contractions in mouse penile tissue (corpora cavernosa). We also compared the effects of PKC activators and inhibitors on contractile responses in mouse corpus cavernosum with those in mouse aorta. Aortic rings and corpus cavernosal strips from C57BL/6J mice were mounted in the organ bath for isometric tension recording. Our data showed that a PKCα/β selective inhibitor, Gö6976 (10 μM), inhibited phenylephrine and 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F (U46619, a thromboxane mimetic)-induced contractions in mouse aorta, reducing the maximum contraction by 94% and 17%, respectively. A non-selective PKC inhibitor, chelerythrine (30 μM), also significantly reduced phenylephrine- and U46619-induced maximum contractions in mouse aorta. However, Gö6976 and chelerythrine had no significant effects on phenylephrine- and U46619-induced contractions in corpus cavernosum. Furthermore, a PKC activator, phorbol-12,13-dibutyrate (0.1 μM), significantly increased contractions in aorta (208 ± 14% of KCl-induced maximum contraction) but failed to cause contractions in corpus cavernosum at 1 and 10 μM. Western blot analysis data suggested that protein expression of PKC was similar in aorta and corpus cavernosum. Taken together, our data indicate that PKC does not have a significant role in agonist-induced contractions in mouse corpus cavernosum, whereas it mediates the contractile response to agonists in the aorta.

Original languageEnglish (US)
Pages (from-to)363-368
Number of pages6
JournalEuropean Journal of Pharmacology
Volume590
Issue number1-3
DOIs
StatePublished - Aug 20 2008

Fingerprint

Protein Kinase C
Aorta
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Phenylephrine
Protein C Inhibitor
Protein Kinase Inhibitors
Phorbol 12,13-Dibutyrate
Thromboxanes
Muscle Contraction
Baths
Inbred C57BL Mouse
Vascular Smooth Muscle
Western Blotting

Keywords

  • Erectile dysfunction
  • Erectile function
  • Erection
  • Penis
  • Protein kinase C
  • Smooth muscle

ASJC Scopus subject areas

  • Pharmacology

Cite this

Comparison of the involvement of protein kinase C in agonist-induced contractions in mouse aorta and corpus cavernosum. / Jin, Liming; Teixeira, Cleber E.; Webb, R Clinton; Leite, Romulo.

In: European Journal of Pharmacology, Vol. 590, No. 1-3, 20.08.2008, p. 363-368.

Research output: Contribution to journalArticle

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abstract = "Protein kinase C (PKC) is involved in the regulation of vascular smooth muscle contraction. However, the role of PKC in erectile function is poorly understood. This study investigated whether PKC mediates agonist-induced contractions in mouse penile tissue (corpora cavernosa). We also compared the effects of PKC activators and inhibitors on contractile responses in mouse corpus cavernosum with those in mouse aorta. Aortic rings and corpus cavernosal strips from C57BL/6J mice were mounted in the organ bath for isometric tension recording. Our data showed that a PKCα/β selective inhibitor, G{\"o}6976 (10 μM), inhibited phenylephrine and 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α (U46619, a thromboxane mimetic)-induced contractions in mouse aorta, reducing the maximum contraction by 94{\%} and 17{\%}, respectively. A non-selective PKC inhibitor, chelerythrine (30 μM), also significantly reduced phenylephrine- and U46619-induced maximum contractions in mouse aorta. However, G{\"o}6976 and chelerythrine had no significant effects on phenylephrine- and U46619-induced contractions in corpus cavernosum. Furthermore, a PKC activator, phorbol-12,13-dibutyrate (0.1 μM), significantly increased contractions in aorta (208 ± 14{\%} of KCl-induced maximum contraction) but failed to cause contractions in corpus cavernosum at 1 and 10 μM. Western blot analysis data suggested that protein expression of PKC was similar in aorta and corpus cavernosum. Taken together, our data indicate that PKC does not have a significant role in agonist-induced contractions in mouse corpus cavernosum, whereas it mediates the contractile response to agonists in the aorta.",
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