Prostanoid receptors mediating contraction in rat, macaque and human bladder smooth muscle in vitro.

Selective prostaglandin EP 1 antagonists have been suggested for the treatment of bladder dysfunction. This study assessed the contractile prostanoid receptor subtypes in human and non-human bladder in vitro. Classical tissue bath studies were conducted using bladder strips exposed to prostanoid agonists and antagonists. Prostaglandin E 2 (PGE 2 ) contracted rat, macaque and human bladder smooth muscle strips (pEC 50 7.91±0.06 ( n =7), 6.40±0.13 ( n =7), and 6.07±0.11 ( n =5), respectively). The EP 1 receptor antagonist, PF2907617 (300 nM), caused a rightward shift of the PGE 2 concentration–response curve in the rat bladder only (p K B 8.40±0.15, n =3). PGE 2 responses in rat and macaque bladders, but not human, were antagonised by the EP 3 antagonist CJ24979 (1 µM). Sulprostone, a mixed EP 1 /EP 3 /FP receptor agonist, induced potent contractions of rat bladder muscle (pEC 50 7.94±0.31, n =6). The FP receptor agonist, prostaglandin F 2α (PGF 2α ), induced bladder contraction in all species tested, but with a lower potency in rat. The selective FP receptor agonist latanoprost caused potent contractions of macaque and human bladder strips only. SQ29548, a selective TP antagonist, and GW848687X, a mixed EP 1 /TP antagonist caused rightward shifts of the concentration–response curves to the selective TP agonist, U46619 (p K B estimates 8.53±0.07 and 7.56±0.06, n =3, respectively). Responses to U46619 were absent in rat preparations. These data suggest significant species differences exist in bladder contractile prostanoid receptor subtypes. We conclude that the EP 1 subtype does not represent the best approach to the clinical treatment of bladder disorders targeting inhibition of smooth muscle contraction. [ABSTRACT FROM AUTHOR]