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The serotonin (5-hydroxytryptamine) 5-HT 7 receptor is up-regulated in Onuf's nucleus in rats with chronic spinal cord injury.
- Source :
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BJU international [BJU Int] 2019 Apr; Vol. 123 (4), pp. 718-725. Date of Electronic Publication: 2018 Jun 15. - Publication Year :
- 2019
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Abstract
- Objectives: To examine the effect of intrathecal (i.t.) serotonin (5-hydroxytryptamine) 5-HT <subscript>7</subscript> agonist administration on voiding function in the urethane-anesthetised rat, and the change in 5-HT <subscript>7</subscript> receptor (5-HT <subscript>7</subscript> R) expression in the lumbosacral cord Onuf's nucleus after spinal cord injury (SCI).<br />Materials and Methods: In all, 32 female Sprague-Dawley (SD) rats were equally divided into a spinally intact (SI) group and SCI group (n = 16 each). At 8 weeks after transection, half of the rats underwent continuous cystometry under urethane anaesthesia, and the 5-HT <subscript>7</subscript> R-selective agonist LP44 was given (i.t.). The remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence, and Western Blot.<br />Results: LP44 administered i.t. had no effect in the SI rats. In SCI rats, LP44 (1-30 μg/kg) induced significant dose-dependent increases in micturition volume, voiding efficiency, number of high-frequency oscillations per micturition; and decreases in residual volume, bladder capacity, peak bladder pressure, threshold pressure and non-voiding contractions. The 5-HT <subscript>7</subscript> R antagonist, SB-269970 (10 μg/kg), partially reversed LP44-induced changes. Using PRV retrograde tracing and immunofluorescence, 5-HT <subscript>7</subscript> Rs were found in the L6-S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly greater in the SCI rats. Western blot showed significantly more 5-HT <subscript>7</subscript> Rs in the ventral L6-S1 spinal cord in SCI rats.<br />Conclusion: A 5-HT <subscript>7</subscript> R agonist, given i.t., improved voiding efficiency in urethane-anesthetised SCI rats, and the 5-HT <subscript>7</subscript> R was significantly up-regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5-HT <subscript>7</subscript> R could be a target for therapeutic interventions.<br /> (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)
- Subjects :
- Animals
Blotting, Western
Chronic Disease
Disease Models, Animal
Female
Injections, Spinal
Rats
Rats, Sprague-Dawley
Receptors, Serotonin physiology
Spinal Cord Injuries pathology
Urination physiology
Receptors, Serotonin drug effects
Serotonin 5-HT2 Receptor Antagonists pharmacology
Spinal Cord Injuries physiopathology
Urination drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1464-410X
- Volume :
- 123
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- BJU international
- Publication Type :
- Academic Journal
- Accession number :
- 29781566
- Full Text :
- https://doi.org/10.1111/bju.14405