Effect of some prostanoid receptor modulators on cholinergic and purinergic pathways in rat model of hemorrhagic cystitis: potential beneficial action of selexipag and alprostadil

Acetylcholine (ACh) and adenosine triphosphate (ATP) are the major neurotransmitters in bladder contraction. This study investigates the modulatory role of some prostanoids in cholinergic and purinergic pathways in normal and cystitis. Cystitis was induced in rats by cyclophosphamide single injection (300 mg/kg) and confirmed histopathologically. Organ bath experiments were implemented using isolated detrusor muscles. Bladder contraction was induced by electrical stimulation and by ACh or ATP direct addition. Cystitis attenuated bladder contractility. Alprostadil and selexipag amplified neurogenic and cholinergic contractions in normal and inflamed bladder. The neurogenic contractions amplification was higher in cystitis with 54.63 ± 42.11% compared to 18.77 ± 5.98% in normal at 10^-7 M selexipag. While cholinergic contraction amplification was higher in cystitis using selexipag and alprostadil, the amplifying effect of 10^-6 M alprostadil was 21.07 ± 15.07% and 128.02 ± 76.61% and the amplifying effect of 10^-6 M selexipag was 39.51 ± 19.72% and 227.6 ± 229.59% in normal and cystitis respectively. At higher concentrations, selexipag and alprostadil amplified purinergic contractions in normal bladder. RO1138452 inhibited neurogenic and cholinergic contractions in normal and inflamed bladder, with less inhibition of cholinergic contractions in inflamed bladder with 26.6 ± 20.72% compared to 54.22 ± 19.6% in normal. The same was observed using SC51322 but cholinergic contraction inhibition was not significant in normal. Both antagonists inhibited purinergic contractions in normal. S18886 inhibited purinergic contractions in normal bladder. EP₁ and IP receptors may play a role in bladder contraction. TP receptor is involved in purinergic signaling in normal physiology. Selexipag and alprostadil may have a potential beneficial action in cystitis and merit further investigation.