EFFECTS OF CAPSAZEPINE AGAINST CAPSAICIN-EVOKED AND PROTON-EVOKED EXCITATION OF SINGLE AIRWAY C-FIBERS AND VAGUS NERVE FROM THE GUINEA-PIG

We have examined the effects of low pH and the selectivity of the caps aicin antagonist capsazepine on single sensory fibres innervating the guinea-pig trachea in vitro, and on the whole isolated vagus nerve. Ap plication of a pH 5 solution for 1 min to the exposed receptive fields of single fibres caused excitation of all C-fibres tested but had no effect on A delta-fibres. Capsazepine (1 mu M) perfused onto the recep tive field for 5 min produced a reversible inhibition of both low pH- and capsaicin (60 nM)-evoked firing of C-fibres. In contrast, capsazep ine had no effect on responses of C-fibres to bradykinin (0.1 mu M) or of A delta-fibres to hypertonic saline. Perfusion of tissues with zer o-calcium Krebs' solution containing trypsin produced denudation of th e epithelium. In these tissues responses to low pH and capsaicin were unchanged and, moreover, the inhibitory effect of capsazepine against low pH and capsaicin was maintained. C- and A delta-fibre responses to bradykinin and hypertonic saline were similarly unaffected by epithel ium removal. Perfusion of the whole guinea-pig vagus nerve with capsai cin (0.3 mu M) or pH 5 buffer caused depolarization. However, in this preparation prior perfusion with capsazepine (1 mu M) abolished respon ses to capsaicin whilst low pH-evoked depolarization was unchanged. Th ese data show that capsazepine is a specific antagonist of proton- and capsaicin-evoked activation of the peripheral endings of sensory nerv es in the guinea-pig airways, and suggest the release by protons of an endogenous ligand for the capsaicin receptor that does not originate from the epithelium.