Time-dependent up-regulation of neuronal 5-hydroxytryptamine binding sites in the detrusor of a rabbit model of partial bladder outlet obstruction
| Autor: | M. R. Dashwood, Robert J. Morgan, Faiz Mumtaz, M.A. Khan, Dimitri P. Mikhailidis, Cecil S. Thompson |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Detrusor muscle Serotonin medicine.medical_specialty Time Factors Urology Urinary Bladder Stimulation Tritium urologic and male genital diseases Blood Urea Nitrogen Electrolytes Bladder outlet obstruction Neurofilament Proteins Internal medicine Muscarinic acetylcholine receptor medicine Animals Neurons Denervation Urinary bladder business.industry Antibodies Monoclonal Muscle Smooth Immunohistochemistry Denervation supersensitivity Up-Regulation Urinary Bladder Neck Obstruction Disease Models Animal Endocrinology medicine.anatomical_structure Creatinine Receptors Serotonin Autoradiography Rabbits business Acetylcholine medicine.drug |
| Zdroj: | World Journal of Urology. 17:255-260 |
| ISSN: | 1433-8726 0724-4983 |
| DOI: | 10.1007/s003450050142 |
| Popis: | Serotonin (5-hydroxytryptamine; 5-HT), a vasoactive bioamine with potent contractile activity, is thought to act indirectly in the urinary bladder by the stimulation of its presynaptic receptors. This results in the release of acetylcholine (ACh), which then acts on muscarinic receptors to produce bladder contractility. Bladder outlet obstruction (BOO) can lead to detrusor instability associated with denervation supersensitivity to ACh. Using a rabbit model of partial BOO, we investigated whether there were any associated changes in the neuronal 5-HT binding sites. Partial BOO was induced in adult male New Zealand White rabbits. Sham-operated age-matched rabbits acted as controls. After 1, 3 and 6 weeks the urinary bladders were excised. Detrusor sections were incubated with [(3)H]-5-HT. Autoradiographs were generated and analysed densitometrically. The presence of nerves was detected using immunohistochemistry with NF200. Autoradiography demonstrated a time-dependent, significant (P0.0001) up-regulation of [(3)H]-5-HT binding sites in the detrusor smooth muscle after the induction of BOO. Immunohistochemistry confirmed that the [(3)H]-5-HT binding sites were neuronal. In the rabbit model of partial BOO there was a significant time-dependent up-regulation of neuronal [(3)H]-5-HT binding sites in the detrusor. This change may influence 5-HT-mediated ACh release, resulting in increased bladder contractility. This, in turn, may play a role in detrusor instability associated with denervation post-junctional supersensitivity. These results provide a possible rationale for further investigation into the use of 5-HT antagonists in the treatment of detrusor instability associated with BOO. |
| Databáze: | OpenAIRE |
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