Central neurotensin nerves modulate colo-colonic reflex activity in the guinea-pig inferior mesenteric ganglion.

1. The effects of neurotensin and of stimulation of preganglionic nerves on peripheral afferent synaptic input from segments of distal colon to neurones in the inferior mesenteric ganglia of guinea-pigs were studied using intracellular recording techniques in vitro. 2. Electrical stimulation of colonic afferent nerve fibres evoked fast, nicotinic synaptic responses (fast EPSPs or action potentials) followed by a slow depolarizing response (slow EPSP). 3. Neurotensin (1 microM) increased the amplitude and duration of slow EPSPs evoked by stimulation of colonic afferents. 4. Distention of a segment of distal colon left attached to an inferior mesenteric ganglion evoked a slow depolarization. Neurotensin (1 microM) increased the amplitude and duration of distention-induced depolarizations. 5. Electrical stimulation of central preganglionic nerve fibres present in the third and fourth lumbar ventral roots increased the amplitude and duration of slow EPSPs evoked by electrical stimulation of colonic afferent nerves. This facilitatory effect was abolished after desensitization to neurotensin. 6. Slow depolarizations evoked by neurotensin and by stimulation of central preganglionic nerves converted subthreshold fast EPSPs due to mechanosensory synaptic input from an attached segment of distal colon to action potentials. This increase in firing rate of sympathetic ganglion cells led to a decrease in colonic intraluminal pressure. 7. Taken together these data support the hypothesis that neurotensin or a closely related substance contained in central preganglionic nerves facilitated release of a non-cholinergic excitatory transmitter from colonic mechanosensory nerves. The slow depolarization evoked by the non-cholinergic transmitter converted on-going subthreshold fast EPSPs to action potentials thereby increasing sympathetic output to the colon. 8. It is suggested that under normal in vivo conditions, central preganglionic fibres containing neurotensin or a closely related peptide modulate peripheral reflex activity through prevertebral ganglia in guinea-pigs.