Modulation of capsaicin-sensitive nerve activation by low pH solutions in guinea-pig lung

We have studied the stimulation of airways sensory nerves by low pH solutio ns and concomitantly induced bronchoconstriction. The effect of low pH buff er and lactic acid solutions at the same pH (5 and 6) were compared and the influence of low pH on the capsaicin effect was recorded. We have used the isolated guinea-pig perfused lung model taking the insufflation pressure a s an indicator of bronchial smooth muscle tone while the calcitonin gene-re lated peptidelike immunoreactivity measured in the lung perfusate represent ed sensory nerves activation. Low pH buffer and lactic acid solution (3 and 4.1 mM) at the same pH of 5 and 6 induced pH-dependent bronchoconstriction and peptides release which were completely abolished after systemic pretre atment with capsaicin. Both responses a ere significantly inhibited after C a2+-free infusion. Capsazepine (10(-6) M), a selective capsaicin antagonist , significantly reduced the calcitonin gene related peptide-like immunoreac tivity overflow evoked by all the solutions studied. Diclofenac (10(-5) M), a cyclooxygenase blocker, inhibited pH 5, pH 6 and lactic acid 3 mM (pH 6) -evoked peptide release, but not lactic acid 3.1 mM (pH 5). The functional response was not significantly modified after diclofenac while only the lac tic acid 3 mM response was significantly reduced by capsazepine. There was a synergistic interaction between capsaicin and low DH buffer on calcitonin gene-related peptide-like immunoreactivity release and an additive effect on bronchoconstriction. It is concluded that in the isolated perfused guine a-pig lung, lactic acid and low pH buffer induced calcitonin gene-related p eptide-like immunoreactivity release and bronchoconstriction by stimulation of capsaicin-sensitive C fibres via a pathway partly dependent of extracel lular Ca2+. The mechanism of calcitonin gene-related peptide-like immunorea ctivity release seems to be the same at pH 6, while differences are evident at pH 5 between low pH buffer and lactic acid. Our results also suggest th at proton activity could exert a modulatory role on the capsaicin-sensitive sensory nerves by a mechanism which remains to be clarified.