Intrinsic and extrinsic inhibitory synaptic inputs to submucous neurones of the guinea-pig small intestine.

1. The sources of inhibitory synaptic inputs to neurones in submucous ganglia of the guinea-pig small intestine were examined by making lesions to cause selective degeneration of nerve terminals of sympathetic or intrinsic origin. Intracellular recordings were used to evaluate the effects of lesions on the inhibitory inputs. Immunohistochemical techniques were used to identify the neurochemical classes of the impaled neurones and to confirm the efficacy of the lesions. 2. The neurones from which recordings were taken were filled with the fluorescent dye Lucifer Yellow. The preparations were then fixed and processed for immunohistochemistry. 3. Thirty-one neurones reactive for vasoactive intestinal polypeptide (VIP) were examined in control submucous ganglia and all exhibited inhibitory synaptic potentials. In preparations extrinsically denervated by severing the mesenteric nerves, twenty-seven of twenty-eight VIP-reactive neurones had inhibitory synaptic potentials. This indicates that these neurones receive inhibitory synaptic inputs from intrinsic neurones. However, significantly more stimuli were required to evoke a detectable inhibitory synaptic potential in extrinsically denervated preparations than in normal intestine. 4. Extrinsic denervations were combined with removal of the myenteric plexus so that nerve terminals arising from both cell bodies in extrinsic ganglia and in the myenteric plexus degenerated. Under these conditions no inhibitory synaptic potentials could be recorded in any of the nine VIP-reactive neurones studied. 5. The conductance change underlying the intrinsic inhibitory synaptic potentials appeared to be similar to that underlying the responses in normal intestine. 6. The time courses of the intrinsic inhibitory synaptic potentials differed from those of the control responses. The responses to short trains of stimuli were significantly briefer and the responses to long trains significantly more prolonged in the extrinsically denervated preparations than in normal preparations. 7. The intrinsic inhibitory synaptic potentials were not significantly affected by phentolamine (0.2 microM), guanethidine (1 microM) or naloxone (1 microM), although the first two drugs markedly depressed control inhibitory synaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS)