TY - JOUR
T1 - Comparison of the involvement of protein kinase C in agonist-induced contractions in mouse aorta and corpus cavernosum
AU - Jin, Liming
AU - Teixeira, Cleber E.
AU - Webb, R. Clinton
AU - Leite, Romulo
N1 - Funding Information:
This study is supported by grants from the American Heart Association (0530007N to LJ) and the National Institutes of Health (DK-73531 to LJ and HL-74167 to RCW). CET was funded by a Postdoctoral Fellowship from the American Heart Association Southeast Affiliate. In the memory of Cleber E. Teixeira, an inspiring young scientist and a wonderful friend and colleague.
PY - 2008/8/20
Y1 - 2008/8/20
N2 - 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 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, 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.
AB - 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 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, 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.
KW - Erectile dysfunction
KW - Erectile function
KW - Erection
KW - Penis
KW - Protein kinase C
KW - Smooth muscle
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U2 - 10.1016/j.ejphar.2008.06.001
DO - 10.1016/j.ejphar.2008.06.001
M3 - Article
C2 - 18614166
AN - SCOPUS:48049118793
SN - 0014-2999
VL - 590
SP - 363
EP - 368
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -