Interactions of Calcium, Prostaglandins and Indomethacin on the Smooth Muscle of the Bladder

Abstract

The effects of prostaglandin (PG) E₂, PGF_2α and indomethacin (Indo) were studied on isolated detrusor smooth muscle strips in balanced salt solution and in 80 mΛf K⁺ depolarizing solution. The addition of Indo to the smooth muscle preparation at concentrations of 0.1 to 1.0 μM 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 m/kf EGTA added PGE₂ or PGF_2α 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 smoth muscle cell membranes.

Potential for control of detrusor smooth muscle spontaneous rhythmic contraction by cyclooxygenase products released by interstitial cells of Cajal

“…The present study is the first to show that rabbit bladder ICCs constitutively express both COX-1 and COX-2, and that selective COX-1 and COX-2 inhibition can exert a potent and highly efficacious inhibition of SRC. These results support and extend earlier reports that indomethacin and other non-selective COX inhibitors reduce SRC in bladder strips isolated from several mammalian species [29,57]. The precise prostaglandin species responsible for initiating SRC was not determined in this study.…”

Phentolamine‐induced rhythmic contractions in bladder detrusor muscle of guinea‐pig

“…It is known that transmembrane Ca2 + -influx plays an essential role in the maintenance of tone and spontaneous contractility and also in the activation of contractions induced by a variety of stimulants in mammalian and human bladders Maggi etal., 1982;Khanna etal., 1983), since these contractile activities are inhibited by Ca2 + entry blockers. In particular, several investigators have demonstrated the inhibitory effect of nifedipine (Ca2 + -entry blocker) or Ca2 + -free medium on the prostaglandin induced contractions in rabbit and human detrusor muscle (Anderson & Kohn, 1978;Forman et al, 1978). It has been suggested that prostaglandins may serve as regulators of Ca2 + binding sites within the cell membrane and thereby modify cell motility (Paton & Daniel, 1967).…”

“…It has been suggested that prostaglandins may serve as regulators of Ca2 + binding sites within the cell membrane and thereby modify cell motility (Paton & Daniel, 1967). Anderson & Kohn (1978) suggested that prostaglandins may act at Ca2 + channels to augment the movement of Ca2 -through membranes or that they might serve a role as carrier for Ca2 + in the rabbit detrusor muscle cells.…”

Positive Inotropic Action of Veratridine in Rat Atria: Possible Involvement of Prostanoids

“…These results may suggest that, in rat atria, veratridine may activate Ca2+ influx across membranes due to the increase in the products of cyclooxygenase pathways. Further, it has been suggested that prostaglandins may act as Ca2+ channels to augment the movement of Ca2+ influx through membranes or that they might serve a role of carrier for Ca2+ in the tissues [8][9][10][11]. These results suggest that veratridine may increase the release of arachidonic acid and subsequently activate the synthesis of pros taglandins, which in turn increase Ca2+ in flux, resulting in the positive inotropic ac tion.…”