The effect of the 5-HT7 serotonin receptor agonist, LP44, on micturition in rats with chronic spinal cord injury
| Autor: | Wu Gang, Yue-min Xu, Jie-min Si, Karl-Erik Andersson, Tu Hongjian, Chen Jasheng, Chen Zhong, Bao-jun Gu |
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| Rok vydání: | 2013 |
| Předmět: |
Agonist
Serotonin receptor agonist medicine.medical_specialty business.industry medicine.drug_class Hydrochloride Urology media_common.quotation_subject Urethral sphincter Antagonist medicine.disease Urination chemistry.chemical_compound chemistry Anesthesia Medicine Neurology (clinical) business Receptor Spinal cord injury media_common medicine.drug |
| Zdroj: | Neurourology and Urodynamics. 33:1165-1170 |
| ISSN: | 0733-2467 |
| Popis: | Aims To better understand the effects of the selective 5-HT7 receptor agonist 4-[2-(Methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-piperazinehexanamide hydrochloride (LP44) on micturition in spinal cord injury (SCI) rats. Methods Female Sprague-Dawley rats weighing 200–275 g were used. SCI was produced in 8 of the 16 rats by transection at the T10 level; cystometric study occurred 8–12 weeks post-transection. Intravesical pressure was monitored in urethane-anesthetized animals via a transvesical catheter. The selective 5-HT7 antagonist (R)-3-[2-[2-(4-Methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl] phenol hydrochloride (SB-269970) was administered after each LP44 dose–response curve (all drugs were administered intravenously, i.v). Results Compared to controls, SCI rats had a higher bladder capacity and residual volume, and a lower voiding efficiency. In SCI rats, LP44 (0.003–0.3 mg/kg, i.v) induced significant dose-dependent increases in micturition volume, significant dose-dependent decreases in residual volume, resulting in significant increases in voiding efficiency. CMG measurements showed a dose-dependent increase of the high-frequency oscillation (HFO) activity, including the number of small oscillation per voiding. This was correlated with the improved voiding efficiency. SB-269970 (0.1 mg/kg, i.v) partially or completely reversed all LP44-induced changes. Conclusions HFOs seems to be correlated with external urethral sphincter (EUS) bursting activity during voiding. Both the bladder voiding efficiency and the periodic EUS activity were decreased in SCI rats. 5-HT7 receptor agonist can enhance HFO activity, thereby improving voiding efficiency. Whether or not these results may have implications for the future treatment of voiding dysfunction in SCI patients remains to be studied. Neurourol. Urodynam. 33:1165–1170, 2014. © 2013 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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