Prokinetic effects of neurokinin-2 receptor agonists on the bladder and rectum of rats with acute spinal cord transection
| Autor: | Edward C. Burgard, Lesley Marson, Karl B. Thor, Mary A. Katofiasc, Nadia M.J. Rupniak |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Urinary Bladder Colorectal pressure Rectum Article Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Pressure Animals NEUROKININ 2 RECEPTOR Receptor Spinal cord injury Spinal Cord Injuries Pharmacology medicine.diagnostic_test Dose-Response Relationship Drug business.industry Cystometry Receptors Neurokinin-2 respiratory system medicine.disease Rats 030104 developmental biology medicine.anatomical_structure chemistry Anesthesia Nasal administration Female Neurokinin A business Gastrointestinal Motility Peptides 030217 neurology & neurosurgery Muscle Contraction |
| Popis: | The suitability of various neurokinin-2 (NK2) receptor agonists and routes of administration to elicit on-demand voiding of the bladder and bowel, as future therapy for individuals with spinal cord injury, was examined using a rat model. The current study examined the feasibility of alternative routes of administration, which are more practical for clinical use than intravenous (IV) administration. Voiding and isovolumetric cystometry were recorded in anesthetized, acutely spinalized, female rats after IV, subcutaneous (SC), intramuscular (IM), intranasal (IN), or sublingual (SL) administration of [Lys5,MeLeu9,Nle10]-NKA(4–10] (LMN-NKA). Administration of LMN-NKA (1–10 μg/kg IV; 10–300 μg/kg SC or IM; 15–1000 μg/kg IN or 300–1,500 μg/kg SL) elicited rapid-onset, short-duration, dose-related increases in bladder pressure and voiding with the rank order for time of both onset and duration being IV < IN < SC = IM < SL. The incidence of voiding was dependent on the dose and route, with all routes resulting in a high voiding efficiency (~70%). Like LMN-NKA, neurokinin A (NKA 1–100 μg/kg IV) and GR 64349 (0.1–30 μg/kg IV or 1–300 μg/kg SC) produced rapid-onset, short-duration increases in bladder pressure, as well as colorectal pressure. Administration of vehicle never produced bladder or rectal contractions or voiding. Transient hypotension was observed after IV injection of LMN-NKA, which was less pronounced after SC injection. Hypotension was not apparent with GR 64349. In conclusion, selective NK2 receptor agonists, administered through various non-IV routes of administration, may provide a safe, convenient, and efficacious method for inducing voiding. |
| Databáze: | OpenAIRE |
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