A non-adrenergic inhibitory nervous pathway in guinea-pig trachea.

1 Electrical stimulation of the guinea-pig isolated tracheal tube causes a biphasic response, initially excitatory and then inhibitory. The excitatory response was abolished by atropine leaving the inhibitory response unaffected.2 The inhibitory response was greatly reduced but not abolished by propranolol or guanethidine. A residual inhibitory response was still present in tracheas in which sympathetic nerve function had been abolished by pretreatment with syrosingopine or 6-hydroxydopamine. These results show that the inhibitory response is predominantly adrenergic but that a small non-adrenergic component is also present.3 The non-adrenergic inhibitory response was abolished by lignocaine and tetrodotoxin suggesting that it is nervous in origin.4 Optimal stimulation parameters for the predominantly adrenergic inhibitory response were a pulse width of 0.7-2 ms, a stimulation period of 7 s and a frequency of 20 Hz. For the non-adrenergic inhibitory response, optimal stimulation parameters were a pulse width of 2 ms, a stimulation period of 12 s and a frequency of 20 Hz.5 Evidence obtained with pharmacological antagonists, enzyme inhibitors and activators suggested that the transmitter mediating the non-adrenergic inhibitory nervous response is unlikely to be: acetylcholine, histamine, 5-hydroxytryptamine, cyclic 3',5'-adenosine monophosphate or a prostaglandin.6 The adenosine uptake blocking drugs dipyridamole, hexobendine and Dilazep potentiated the non-adrenergic inhibitory nervous response and unmasked inhibitory responses to adenosine and adenosine 5'-triphosphate.7 It is concluded that electrical stimulation of the guinea-pig trachea, in addition to activating cholinergic and adrenergic nervous pathways, may activate a separate and distinct inhibitory nervous pathway. This pathway has some features in common with the non-adrenergic non-cholinergic inhibitory pathways in gastro-intestinal muscle.