The effect of K+ channel openers on submucosal gland function and epithelial transport of the ferret trachea, in vitro.
The effects of three K+ channel openers on lysozyme output from submucosal gland serous cells and epithelial albumin transport following maintained submaximal stimulation by the secretagogues methacholine and phenylephrine were examined in the ferret trachea in vitro preparation. The K+ channel openers Ro 31-6930, 2-(6-cyano-2,2-dimethyl-2H-1-benzopyran-4-yl)-pyridine 1-oxide (10 nM-10 microM), levcromakalim, BRL38227 (10 nM-10 microM) and pinacidil (100 nM-10 microM) produced a concentration dependent inhibition of (20 microM) methacholine-induced lysozyme output, with pD2 values of 7.64, 7.72 and 7.28 respectively. Ro 31-6930 (10 nM-10 microM), levcromakalim (10 nM-10 microM) and pinacidil (1 nM-10 microM) also produced a concentration dependent inhibition of (100 microM) phenylephrine-induced lysozyme output, with pD2 values of 7.64, 6.55 and 9.16 respectively. Furthermore, glibenclamide (1 microM) produced a modest attenuation of the K+ channel opener effects on secretagogue-induced lysozyme output. All three K+ channel openers failed to produce any significant change in either methacholine or phenylephrine-induced albumin outputs. The K+ channel openers exerted marked effects on airway secretion processes, suggesting that these compounds may have an antisecretory effect. The relevance of the use of the K+ channel openers in airway disease remains to be determined.
Griffin
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A
Department of Physiology, St George's Hospital Medical School, London, UK.
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019806:Cromakalim; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005289:Ferrets; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009113:Muramidase / Q000187:drug effects / Q000378:metabolism*; D009130:Muscle, Smooth / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000201:enzymology
D000418:Albumins; D001578:Benzopyrans; D001993:Bronchodilator Agents; D015221:Potassium Channels; D011725:Pyridines; D011758:Pyrroles; D019806:Cromakalim; D016210:Methacholine Chloride; C062764:Ro 31-6930; D010656:Phenylephrine; D009113:Muramidase