Prostaglandin involvement in contractions evoked in rabbit detrusor by field stimulation and by adenosine 5′-triphosphate

Previous reports suggest that in rabbit urinary bladder both noncholinergic nonadrenergic excitatory responses and the contraction produced by adenosine 5′-triphosphate (ATP) are antagonized by indomethacin. We have attempted by further indirect testing on isolated detrusor strips to determine what role prostaglandins (PGs) might play in these processes. The second part of the biphasic contractile response to ATP was reduced to about 30% of control by PG synthesis inhibitors but the initial phase of the ATP response and the contraction produced by the β, γ-methylene analogue of ATP were unaffected. At concentrations that did not affect the response to acetylcholine but greatly suppressed the response to arachidonic acid, indomethacin antagonized the contraction evoked by field stimulation by about 30% at 1–2 Hz (largely noncholinergic and nonadrenergic). SC 19220, a putative PG receptor blocker, also produced about 25% reduction in the response to field stimulation but with only about 50% reduction in the response to arachidonic acid, PGE2, or PGF2α. SC 19220 also antagonized the frequency – response curve in atropine-treated strips. These findings lead us to suggest that besides maintaining tone and spontaneous activity in the bladder PGs mediate the slow tonic phase of the ATP response and may contribute to facilitatory modulation of noncholinergic nonadrenergic excitatory transmission.