Different effects of the K+ channel blockers 4-aminopyridine and charybdotoxin on sensory nerves in guinea-pig lung.
In the isolated guinea-pig bronchus, the potassium channel blocking agent 4-aminopyridine (10(-4) M) caused a contraction which was abolished by capsaicin tachyphylaxis, suggesting involvement of sensory neuropeptides. Charybdotoxin (10(-8), 5 x 10(-8) M), which is a potent blocker of the high-conductance Ca(2+)-activated K+ channel in smooth muscle, caused slowly developing and long lasting bronchoconstriction, which was resistant to capsaicin tachyphylaxis. Neither 4-aminopyridine (10(-3), 10(-4) M) nor charybdotoxin (10(-8), 5 x 10(-8) M) had any significant effect on the bronchoconstriction induced by electrical field stimulation. Furthermore, charybdotoxin had no significant influence on the inhibitory effect of the alpha 2-adrenoceptor agonist SKF 35886 (5 x 10(-7) M) on the bronchoconstriction induced by electrical field stimulation. In the isolated perfused guinea-pig lung, 4-aminopyridine (3 x 10(-5) -10(-3) M) caused bronchoconstriction and enhanced both basal and (at 3 x 10(-5) M) vagal nerve stimulation-evoked calcitonin gene-related peptide outflow from pulmonary sensory nerves. In conclusion, 4-aminopyridine stimulated capsaicin-sensitive sensory neurons and enhanced the sensory activation induced by vagal nerve stimulation in guinea-pig lung. Charybdotoxin, on the other hand, caused bronchial contraction independently of capsaicin-sensitive nerves.
Lou
Y P
YP
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Lundberg
J M
JM
D015761:4-Aminopyridine / Q000494:pharmacology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000294:innervation; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000494:pharmacology; D018999:Charybdotoxin; D004558:Electric Stimulation; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000294:innervation*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects*; D012604:Scorpion Venoms / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; C035857:xylonidine; D001285:Atropine; D015761:4-Aminopyridine; D015740:Calcitonin Gene-Related Peptide; D006145:Guanethidine