Evidence for a prostaglandin link in the purinergic activation of rabbit bladder smooth muscle

Two independent pathways for contraction coupling are described for the cholinergic and ATP activation of rabbit detrusor smooth muscle. Both ATP (0.1 mM) and carbachol (1.0 microM) promote contraction of the rabbit detrusor muscle that can be selectively blocked, the cholinergic activation with atropine and an ATP-induced sustained contraction with indomethacin (indo). Both agonists promoted uptake of 45Ca, but they mediate this response separately because atropine will not effectively block ATP Ca++ uptake but will block carbachol Ca++ uptake. Indo will block the sustained contraction produced by ATP, but will abolish a rapid phasic twitch-like contraction induced by ATP. Indo, however, will partially block Ca++ uptake induced by ATP. Radioimmunoassay for prostaglandin (PG) E in bath perfusate showed that ATP markedly increased synthesis of PGE and this effect was sharply reduced by indo and only partially affected by atropine. This suggests a direct link between the purinergic activation and an increased synthesis of PGE that was indo-sensitive and therefore associated with the sustained ATP-induced contraction. It was further shown that PGE was the probable PG that was released by ATP stimulation rather than PGF2 alpha because radioimmunoassay for PGF2 alpha gave low and inconsistent measurements.