Comparison of endothelin-1-mediated tissue tension and calcium mobilization effects in isolated rabbit corpus cavernosum.
OBJECTIVE
To directly compare and contrast the effects of endothelin-1 (ET-1) and adrenoreceptor agonists norepinephrine and phenylephrine on eliciting calcium influx in primary rabbit corpus cavernosum cells and their ability to elicit tissue contractions. The potent vasoconstrictor peptide ET-1 and the alpha-adrenoreceptor agonists are important modulators of smooth muscle tone in the penile corpus cavernosum. However, the mechanisms involved in maintaining smooth muscle tone and contraction are not clearly understood.


METHODS
Intracellular calcium mobilization was measured in cultured corpus cavernosum smooth muscle cells using calcium-sensing dyes in conjunction with a fluorometric imaging plate reader. Tissue tension studies on rabbit corpus cavernosum were conducted using organ chambers.


RESULTS
ET-1 at concentrations as low as 10 nM was sufficient to induce a transient increase of intracellular calcium in these cells. In contrast, concentrations of 1 mM and greater of norepinephrine and phenylephrine were required to elicit comparable calcium fluxes in cavernosum cells. Tissue bath studies indicated that ET-1 is a potent stimulator of corpus cavernosum smooth muscle contraction, with concentrations as low as 10 nM sufficient to initiate contraction.


CONCLUSIONS
The potency of ET-1 in producing contraction on tissue strips and inducing calcium flux suggests that ET-1 might be an important mediator for modulating and maintaining corpus cavernosum smooth muscle tone. Therefore, additional exploration of the role of endothelins and their receptors in the tumescence and detumescence states of the penis would be extremely valuable.
Abeysinghe
Harindra R
HR
Department of Reproductive Therapeutics, Johnson & Johnson Pharmaceutical Research & Development, Raritan, New Jersey 08869, USA.
Clancy
Joanna
J
Qiu
Yuhong
Y
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010413:Penis / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D002118:Calcium; D009638:Norepinephrine