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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.