Interactions of calcium, prostaglandins and indomethacin on the smooth muscle of the bladder.

The effects of prostaglandin (PG) E2, PGF2alpha and indomethacin (Indo) were studied on isolated detrusor smooth muscle strips in balanced salt solution and in 80 mMK+ depolarizing solution. The addition of Indo to the smooth muscle preparation at concentrations of 0.1 to 1.0 micronM produced depression of spontaneous motility that was partially antagonized by PGE2 or by elevating the extracellular Ca2+ level. Alone, both PGE2 and Ca2+ caused a marked increase in motility, increasing both frequency and amplitude. In low Ca2+, K+ depolarized bathing medium with 0.1 mM EGTA added PGE2 or PGF2alpha augmented Ca2+ contractures both in velocity and amplitude while either PG without Ca2+ had no effect on the smooth muscle. Indo produced a noncompetitive antagonism of the Ca2+ dose response curve in 80 mM K+ depolarized preparations suggesting a direct effect on Ca2+ flux. Also Indo depressed both PG and Ca2+ contractures in terms of velocity and magnitude, suggesting that Indo may act at Ca2+ channels in addition to its action on PG synthetase. These data support the work of others who suggest that PGs may augment Ca2+ permeability, acting at the Ca2+ channel or as a carrier for Ca2+ across smooth muscle cell membranes.