1. Electrical stimulation (2-50Hz) of mesenteric nerves of the guinea-pig isolated ileum resulted in contraction of preparations pretreated with adrenergic neuron blocking agents (guanethidine, bretylium), or on preparations obtained from animals pretreated with reserpine. Stimulation at low frequencies (2-10 Hz) also caused contraction in untreated preparations. 2. The response was abolished by hyoscine (1 ×10-7-1×10-6 g/ml) or morphine (2×10-7 g/ml). However, previous bilateral vagotomy, hexamethonium (1×10-4 g/ml), mecamylamine (1×10-5 g/ml), or desensitization of the gut to 5-HT caused practically no inhibition. 3. Capsaicin inhibited or abolished (IC50 1.5 ×10-8 g/ml) the contraction elicited by stimulation of mesenteric nerves in an irreversible manner. The drug did not inhibit the contraction to field stimulation of the postganglionic cholinergic fibres. 4. Neither the contraction of the duodenum to stimulation of the preganglionic vagal fibres, nor the adrenergic inhibition elicited by periarterial nerve stimulation were influenced by capsaicin. 5. It is concluded that the cholinergic response described above is neither parasympathetic in origin nor can it explained on the basis of a cholinergic mechanism in adrenergic neurotransmission (Burn's theory). A hypothesis is put forward that nerve fibres characterized by their specific sensitivity to capsaicin, presumably originating from sensory neurons excite cholinergic neurons of the myenteric plexus.
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