Role of BK(Ca) channels and cyclic nucleotides in synergistic relaxation of trachea.
beta-Adrenoceptor agonists, nitric oxide (NO), and NO donors have been shown to mediate their effects through large conductance Ca(2+)-activated K(+) (BK(Ca)) channels. The mechanism of the synergistic effect of the beta(2)-adrenoceptor agonist, salbutamol, and an NO donor, sodium nitroprusside, was studied in guinea pig tracheal preparations. Salbutamol (0.1 nM) and sodium nitroprusside (0.33 microM) alone relaxed the acetyl-beta-methylcholine chloride (methacholine)-contracted preparations only by 0.5% and 28%, respectively, but their combination caused a maximum of 60% relaxation (at 3 min), which stabilized to 40% (at 10 min). Iberiotoxin, a selective inhibitor of the BK(Ca) channels, did not abolish the synergistic effect. 3-isobutyl-1-methylxanthine (IBMX) did not modify relaxation evoked by the drugs. Concentrations of cyclic nucleotides did not correlate with relaxations as a function of time. The mechanism of synergy remains to be clarified. The results show that NO is an important modulator in the relaxation of guinea pig trachea induced by beta(2)-adrenoceptor agonists in vitro.
Vaali
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K
Institute of Biomedicine, Department of Pharmacology and Toxicology, Siltavuorenpenger 10 A, FIN-00014 University of Helsinki, Helsinki, Finland. kirsi.vaali@helsinki.fi
Li
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L
Lähteenmäki
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T
Vapaatalo
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis / Q000502:physiology*; D006152:Cyclic GMP / Q000032:analysis / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D009599:Nitroprusside; C064719:iberiotoxin; D000242:Cyclic AMP; D006152:Cyclic GMP; D000420:Albuterol; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine