Different ion channel control pH6-induced bronchoconstriction and calcitonin gene-related peptide release in the guinea-pig lung

We have studied the bronchoconstriction and the release of calcitonin gene- related peptide-like immunoreactivity induced by perfusion of pH6 buffer in the isolated guinea-pig perfused lung. Both bronchoconstriction and peptid e release were completely abolished after systemic capsaicin pretreatment. Ca2+-free pH6 buffer infusion also completely inhibited the bronchial respo nse, whereas the calcitonin gene-related peptide-like immunoreactivity over flow was significantly reduced, omega-Conotoxine and omega-agatoxin IVA kno wn as N-, L- and P-type Ca2+ channel blocker, respectively, and the Na+ cha nnel blocker tetrodotoxin decreased significantly the pH6-induced bronchial response and calcitonin gene-related peptide like immunoreactivity overflo w Nifedipine was without influence suggesting the involvement of both P- an d N-type Ca2+ channel as well as the activation of an axon reflex. Rutheniu m red had a more pronounced reduction effect on the functional response tha n on the peptide release. Ryanodine and caffeine are both agents known to i nfluence Ca2+ release from sarcoplasmic reticulum. Ryanodine significantly reduced both bronchoconstriction and calcitonin gene-related peptide-like i mmunoreactivity overflow Caffeine as well as theophylline and the Na+-H+ bl ocker, dimethylamiloride, largely depressed the functional response while p roducing a significant increase of calcitonin gene-related peptide-like imm unoreactivity basal value. The pH6-induced peptide overflow was slightly in hibited after caffeine and dimethylamiloride pretreatment whereas no signif icant change was observed after theophylline. It is concluded that multiple ion channels including different type of Ca2+ channels appear to participa te in pH6-induced bronchoconstriction and calcitonin gene-related peptide-l ike immunoreactivity release in the guinea-pig lung.