Modulation of Ca2+ sensitivity regulates contractility of rabbit corpus cavernosum smooth muscle.
OBJECTIVE
We examined the role of the modulation of Ca2+ sensitivity for regulating the contractility of corpus cavernosum smooth muscle.


METHODS
We applied simultaneous measurements of intracellular Ca2+ concentration and tension in fura-PE3 loaded intact strips and receptor coupled permeabilization by alpha-toxin.


RESULTS
In intact fura-PE3 loaded strips the tension induced by 10 microM. 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 microM. phenylephrine the application of 10 microM. Y-27632 (a Rho kinase inhibitor) induced relaxation with a slight decrease in intracellular Ca2+ concentration, while the application of 3 microM. GF109203X (a protein kinase C inhibitor) induced relaxation without changing intracellular Ca2+ concentration. In alpha-toxin permeabilized strips 10 microM. 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.
Takahashi
Ryosuke
R
Division of Molecular Cardiology, Research Institute of Angiocardiology and Department of Urology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Nishimura
Junji
J
Hirano
Katsuya
K
Naito
Seiji
S
Kanaide
Hideo
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010413:Penis / Q000378:metabolism / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D010738:Type C Phospholipases / Q000494:pharmacology; D054460:rho-Associated Kinases
D000316:Adrenergic alpha-Agonists; D000577:Amides; D004791:Enzyme Inhibitors; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D008301:Maleimides; D011725:Pyridines; C108830:Y 27632; D010656:Phenylephrine; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; C070515:bisindolylmaleimide I; D002118:Calcium