The modulation of CA2+ sensitivity regulates contractility of rabbit corpus cavernosum smooth muscle

Ryosuke Takahashi, Junji Nishimura, Katsuya Hirano, Seiji Naito, Hideo Kanaide

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Abstract

Purpose: We examined the role of the modulation of Ca2+ sensitivity for regulating the contractility of corpus cavernosum smooth muscle. Materials and Methods: We applied simultaneous measurements of intracellular Ca2+ concentration and tension in fura-PE3 loaded intact strips and receptor coupled permeabilization by α-toxin. Results: In intact fura-PE3 loaded strips the tension induced by 10 μM. phenylephrine was significantly greater than that produced by depolarization with 118 mM. K+, although the extent of intracellular Ca2+ concentration elevations was similar. During sustained contraction induced by 10 μM. phenylephrine the application of 10 μM. Y-27632 (a Rho kinase inhibitor) induced relaxation with a slight decrease in intracellular Ca2+ concentration, while the application of 3 μM. GF109203X (a protein kinase C inhibitor) induced relaxation without changing intracellular Ca2+ concentration. In α-toxin permeabilized strips 10 μM. phenylephrine induced a larger increase in force at a constant intracellular Ca2+ concentration and produced a leftward shift in the intracellular Ca2+ concentration-tension relationship, a response that was partially inhibited by pretreatment with Y-27632 or GF109203X. Conclusions: These results indicate that in rabbit corpus cavernosum smooth muscle phenylephrine induces contraction not only by increasing intracellular Ca2+ concentration, but also by increasing Ca2+ sensitivity of the contractile apparatus in a Rho kinase and protein kinase C dependent manner. Antagonism of Ca2+ sensitization pathways in the corpus cavernosum smooth muscle represents an alternate target for the treatment of erectile dysfunction.

Original languageEnglish
Pages (from-to)2412-2416
Number of pages5
JournalJournal of Urology
Volume169
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

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All Science Journal Classification (ASJC) codes

  • Urology

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