| Autor: |
Digavalli V, Sivarao, Kimberly, Newberry, Shaun, Langdon, Alicia V, Lee, Piyasena, Hewawasam, Mary Jane, Plym, Laura, Signor, Robert, Myers, Nicholas J, Lodge |
| Rok vydání: |
2005 |
| Předmět: |
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| Zdroj: |
The Journal of pharmacology and experimental therapeutics. 313(2) |
| ISSN: |
0022-3565 |
| Popis: |
We evaluated the effects of 4-(5-chloro-2-hydroxyphenyl)-3-(2-hydroxyethyl)-6-(trifluoromethyl)-quinolin-2(1H)-one (BMS-223131), an opener of large conductance Ca(2+)-activated potassium (maxi-K) channels, on normal and stress-exacerbated colonic motility and visceral nociception in the rat. Fecal output was employed as an index of motility. Visceral nociception, in response to intracolonic balloon distension (10-90 mm Hg; 30 s duration), was evaluated using one of three indices: change in blood pressure, abdominal withdrawal, or myoelectrical activity. BMS-223131 (2, 6, or 20 mg/kg i.p.) produced a small but dose-dependent and significant reduction in cumulative 24-h fecal output. Fecal output in response to stress (1-h restraint plus bursts of air to the face) was markedly inhibited by BMS-223131, and moisture content was significantly reduced. With regard to visceral pain, the transient and distention-dependent reduction in arterial pressure in anesthetized animals was inhibited by BMS-223131 in a dose-dependent manner. Distension-induced abdominal withdrawal in conscious rats was also dose-dependently attenuated by BMS-223131. BMS-223131 at a dose of 20 mg/kg markedly attenuated the increase in myoelectrical activity evoked by balloon distention in conscious animals. BMS-223131 was also evaluated in viscerally hypersensitive rats (sensitized as neonates by intracolonic mustard oil) where it produced a robust dose-dependent attenuation of the abdominal withdrawal response. Compared with naive animals, BMS-223131 was more potent in the sensitized animals. Thus, BMS-223131 effectively reduced stress-induced colonic motility and visceral nociception supporting the potential utility of maxi-K channel openers for the treatment of bowel disorders involving dysfunctional motility and visceral sensitivity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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