Effect of 5-HT7 receptor agonist, LP-211, on micturition following spinal cord injury in male rats.

Am J Transl Res

Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical SciencesTehran, Iran; Experimental Medicine Research Center, School of Medicine, Tehran University of Medical SciencesTehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical SciencesTehran, Iran.

Published: July 2016

AI Article Synopsis

  • The study investigates the impact of a 5-HT7 receptor agonist, LP-211, on the micturition reflex in rats with spinal cord injuries.
  • Following spinal injury, the administration of LP-211 led to increased bladder capacity and voiding efficiency, indicating a positive effect on urine elimination.
  • The findings suggest that activating 5-HT7 receptors enhances micturition, highlighting their significance in regulating urinary function after spinal injuries.

Article Abstract

Background And Purpose: Central and peripheral 5-hydroxytryptamine (5-HT) receptors play a critical role in regulation of micturition reflex. The aim of this study was to evaluate effect of a 5-HT7 receptor agonist, LP-211 (N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide) on micturition reflex in acute spinal cord-injured (SCI) rats during infusion of vehicle into the bladder.

Methods: SCI was induced by compressing T10 segment using an aneurysm clip, extradurally in male rats. Following two weeks, LP-211 doses (0.003-0.3 mg/kg) were administered cumulatively (intraperitoneally, i.p.) with 20 min interval. The 5-HT7 antagonist, SB-269970 ((R)-3-[2-[2-(4-Methylpiperidin-1-yl) ethyl] pyrrolidine-1-sulfonyl] phenol hydrochloride), was administered after achievement of LP-211 dose-response. A cystometric study was performed 2 weeks after spinal crushing in all the animals. Cystometric variables consisting of micturition volume (voided volume), residual volume (volume remaining in the bladder after voiding), and bladder capacity (micturition volume plus residual volume). Voiding efficiency was calculated as the percent of micturition volume to bladder capacity.

Findings: Intact and sham-operated rats showed few significant changes in micturition reflex. SCI rats responded to LP-211 (0.003-0.3, mg/kg, i.v.) with dose-dependent increases in bladder capacity, and residual volume. In this treatment group, LP-211 induced significant dose-dependent increases in micturition volume, resulting in significant increases in voiding efficiency (P<0.001) compared to intact and sham-operated rats, SB-269970 (0.1 mg/kg, i.v.) completely reversed the LP-211-induced changes on micturition volume and voiding efficiency was decreased significantly.

Conclusion: The 5-HT7 receptors activation by LP-211 facilitated the micturition reflex. Furthermore, 5-HT7 receptors do seem to play an important role in physiological regulation of micturition, and as a result, may represent a new strategy to improve voiding efficiency after SCI in patients in the future perspective.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931148PMC

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