Effects of NS1608, a BKCachannel agonist, on the contractility of guinea-pig urinary bladderin vitro
| Autor: | Ticiana Camila Mora, Guilherme Suarez-Kurtz |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Pharmacology
Detrusor muscle medicine.medical_specialty Chemistry Ryanodine receptor Potassium channel blocker Iberiotoxin Apamin Potassium channel Contractility chemistry.chemical_compound Endocrinology medicine.anatomical_structure Internal medicine medicine medicine.symptom medicine.drug Muscle contraction |
| Zdroj: | British Journal of Pharmacology. 144:636-641 |
| ISSN: | 0007-1188 |
| Popis: | 1 The functional effects of NS1608 ((N-(3-(trifluoromethyl)phenyl)-N′-(2-hydroxy-5-chlorophenyl)urea), an opener of the large conductance, Ca2+-activated K+ (BKCa) channel, on the contractility of guinea-pig urinary bladder muscle are described. 2 NS1608 (0.3–30 μM) had no significant effect on the integrated myogenic activity (tension integral) or the electrically evoked twitches of detrusor muscle strips. Possible mechanisms for the discrepancy between the lack of functional effects of NS1608 per se on detrusor contractility and this drug's agonistic effect on BKCa currents in isolated bladder myocytes are discussed. 3 4-Aminopyridine (1 mM), a blocker of voltage-gated K+ (KV) channels, increased the tension integral 2.7-fold, on average. NS1608 (30 μM) counteracted this effect. 4 Apamin (100 nM), a selective blocker of the small conductance, Ca2+-activated K+ (SKCa) channel, increased the tension integral 1.7-fold, on average. This effect was reversed by NS1608 (30 μM). 5 Ryanodine (10 μM), a modulator of the sarcoplasmic reticulum (SR) Ca2+-release channel, increased the tension integral 1.9-fold, on average. This effect was reversed by NS1608 (30 μM). 6 Iberiotoxin (IbTX, 50 nM), a selective blocker of the BKCa channel, caused additional increases in the tension integral of detrusor strips pretreated with apamin or ryanodine and prevented the inhibitory effects of NS1608 (30 μM) in detrusor contractility. 7 The present study shows that blockade of repolarizing currents carried by, respectively apamin- and 4-aminopyridine-sensitive K+ channels unmasks an activation of BKCa in guinea-pig urinary bladder smooth muscle strips. British Journal of Pharmacology (2005) 144, 636–641. doi:10.1038/sj.bjp.0706034 |
| Databáze: | OpenAIRE |
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