Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats.

Abstract

Adenosine triphosphate (ATP) (Sigma Chemical Co., St. Louis, Missouri) is known to contract animal as well as human detrusor muscle and recent investigations have shown an involvement of ligand gated purinergic-1 receptors in detrusor contraction. In addition, ligand gated purinergic-3 receptors have been demonstrated on suburothelial sensory nerves (C-fibers) and may be involved in distention induced initiation of the micturition reflex. We tested the hypothesis that ATP given intravesically can stimulate afferent nerves and initiate the micturition reflex. Continuous cystometry was performed in conscious, freely moving, normal female Sprague-Dawley rats. Cystometric parameters were evaluated before and after drug administration. Instilled intravesically ATP (10 mM.) induced bladder overactivity in 6 animals with a mean increase in voiding pressure plus or minus standard error of 73 +/- 9 to 107 +/- 9 cm. water (p <0.01), mean baseline pressure increase of 5.32 +/- 0.58 to 12.71 +/- 1.01 cm. water (p <0.01) and mean bladder capacity decrease of 1.13 +/- 0.25 to 0.75 +/- 021 ml. (p <0.01). Lower concentrations had no significant effect. The effects of ATP were abolished by pretreatment with the ganglion blocker hexamethonium (40 mg./kg. ), nitric oxide synthase substrate L-arginine (Sigma Chemical Co.) (200 mg./kg. ) and neurokinin-2 receptor antagonist 123 (S)-N-methyl-N 123 4-(acetylamino-4-phenyl piperidone)-2-(3,4-dichlorophenyl) butyl 125 benzamide (Molecular Probes, Leiden, The Netherlands) (4 nmol.) given intravenously, the ligand gated purinergic-3 antagonist 2'-(or 3')-O-(trinitrophyl)adenosine 5'-triphosphate (50 microM./kg.) given intravenously and the k channel opener ZD6169 given intravesically.(ATP). ATP given intravesically can induce bladder overactivity, probably by stimulating suburothelial C-fibers. The data suggest that several mediators and mechanisms are involved in mechano-afferent transduction in the bladder.