The present experiments were designed to investigate the effects of omepraz
ole, a H+-K+ ATPase inhibitor, on corporal smooth muscle tone in vitro. All
spontaneous contractile activity in the corpus cavernosum was blocked foll
owing omeprazole (0.1 mM-1 mM) administration. However atropine (1 mu M), N
-w-nitro L-arginine methyl ester (L-NAME, 30 mu M) or indomethacin (10 mu M
) did not affect the spontaneous contraction. Omeprazole (10 mu M-1 mM) con
centration-dependently induced relaxation in corporal smooth muscle precont
racted with 10 mu M phenylephrine or 80 mM KCI. Pretreatment of corporal ti
ssue with L-NAME (30 mu M) indomethacin (10 mu M), ammonium chloride (7.5 m
M), sodium acetate (7.5 mM), tetraethyl ammonium chloride (0.5 mM) or glibe
nclamide (1 mu M) had no effect on the omeprazole induced relaxant response
s. Nimodipine, an L-type Ca++ channel blocker relaxed corporal strips preco
ntracted with 80 mM KCI. Collectively, these results indicate that the inhi
bition of spontaneous Contraction and the relaxation of precontracted corpo
ral smooth muscle by omeprazole is probably mediated by the blockade of cal
cium channels. Further work is needed to determine the cellular mechanism(s
) of action by which omeprazole acts on corpus cavernosum smooth muscle.