We investigated the existence of endothelin (ET) receptor subtypes in airway neurones from the rat and guinea-pig and determined the ability of these receptors to modulate contractile function. Rat tracheal neuron cultures as well as rat and guinea-pig whole mount preparations were labelled with antibodies to the cholinergic nerve marker choline acetyltransferase (ChAT), the neuron specific marker protein gene product 9.5 (PGP 9.5) and to ETA and ETB receptors. Following incubation with fluorescent secondary antibodies, fluorescence was detected using confocal microscopy with dual emission protocols. Specific fluorescence was detected both in whole mount preparations and neuron cultures, in association with the primary antibodies. Specific fluorescence associated with either ETA and ETB receptors was colocalized with that for PGP 9.5. Despite the presence of ETA and ETB receptors on airway nerves, ET-1 failed to significantly alter cholinergic, excitatory or inhibitory non-adrenergic-non-cholinergic nerve-mediated responses in guinea-pig airways. This is in sharp contrast to ET-1-induced potentiation of responses to cholinergic nerve-evoked contraction in rat trachea. Thus, although ETA and ETB receptors exist in airway cholinergic neurons in whole mount preparations and in primary neuron cultures from rat and guinea-pig trachea, the influence of these receptors on contractile function appears to be species-dependent. (C) 1999 Academic Press.