Endothelin-1 as a putative modulator of erectile dysfunction. II. Calcium mobilization in cultured human corporal smooth muscle cells.

Abstract

To gain mechanistic insight into the actions of endothelin-1 (ET-1) in human erectile tissue. Fura-2 based digital imaging microscopy was used to measure intracellular calcium levels in discrete cellular regions (cytosol and nucleus) in single cultured human corporal smooth muscle cells derived from corporal tissue excised from 3 patients with organic erectile dysfunction, as well as 2 patients with documented erections. Endothelin-1 elicited a transient and concentration-dependent increase in cytosolic and nuclear calcium levels in cells from both patient populations. However, while the peak amplitudes of the ET-1-induced cytosolic calcium increases were similar in cells from the 2 patient populations, the observed increases in nuclear calcium levels were much more pronounced in cells from patients with organic erectile dysfunction than in patients with documented erections. Endothelin-1, by virtue of its ability to increase both cytosolic and nuclear calcium levels, may serve not only as a critical determinant of corporal tissue tone, but also as a modulator of cellular proliferation and phenotypic expression.