The electrophysiological effects of neurotensin on neurones of guinea‐pig prevertebral sympathetic ganglia.

Abstract

SUMMARY1. The membrane effects of neurotensin on neurones of guinea-pig prevertebral ganglia were investigated by means of intracellular recording techniques in vitro.2. Neurotensin (2-5 ,UM) applied by superfusion caused depolarizing responses in fifty-seven of seventy-four neurones tested in the inferior mesenteric ganglion and thirty-seven of forty-seven neurones tested in the coeliac plexus. The remaining neurones tested showed no membrane response.3. Responses to neurotensin could be discriminated into two different types of membrane depolarizations on the basis of their different time courses and pharmacological characteristics: a steady-state type of depolarization and a transient type of depolarization. Seven of fifty-seven responsive neurones tested in the inferior mesenteric ganglion and ten of thirty-seven responsive neurones tested in the coeliac plexus responded to neurotensin with a depolarization which was maintained constant as long as neurotensin was superfused over the preparation (steady-state type). Forty-eight of fifty-seven responsive neurones tested in the inferior mesenteric ganglion and twenty of thirty-seven responsive neurones tested in the coeliac plexus responded with a transient depolarization which was followed by a repolarization in the maintained presence of neurotensin (transient type). A combination of both types of responses was observed in two neurones tested in the inferior mesenteric ganglion and in seven neurones tested in the coeliac plexus.4. Steady-state type responses were characterized by a slowly developing membrane depolarization which reached a plateau and lasted throughout the presence of neurotensin. Amplitude and time course of this response were not altered in a solution containing hexamethonium (10 ram) and atropine (10 tM) or by a solution low in calcium (1 mM) and high in magnesium (15 mM).5. Transient type depolarizations evoked by neurotensin were faster in reaching their maximum and were followed by a repolarization during the maintained presence of neurotensin. Responses similar in time course and amplitude were obtained in solutions containing hexamethonium (10-100 /tM) and atropine (10 /IM).However, transient responses were abolished in a solution low in calcium (1 mM) and high in magnesium (15 mM) and were markedly attenuated in ganglia treated with capsaicin (3 /tM). 7. Both types of depolarizations were observed when the C-terminal hexapeptide fragment neurotensin 8-13 was used.8. It was concluded that neurotensin caused an increase in excitability in a large portion of prevertebral sympathetic neurones of guinea-pigs by interaction with receptors specific for the C-terminal, bioactive portion of the molecule. The response of the large majority of neurones was mediated through Ca2+-dependent release of a non-cholinergic excitatory transmitter from capsaicin-sensitive nerve terminals.

Neurotensin facilitates release of substance P in the guinea‐pig inferior mesenteric ganglion.

“…The mean resting membrane potential of these neurones was -53 0 + 1-6 mV, a value similar to one reported previously for ganglion cells in guinea-pig inferior mesenteric ganglia (Stapelfeldt & Szurszewski, 1989). When neurotensin8-'3 (5 aM) 329 W. H. STAPELFELDT AND J. H. SZURSZEWSKI was superfused over these ganglia, fourteen neurones (67 %) responded with a slow depolarization which averaged 4-3 + 0-8 mV in amplitude.…”

“…Bipolar platinum electrodes were attached to the lumbar colonic nerve and connected to a stimulus isolation unit (Grass SIU5A) and stimulator (Grass S88). Intracellular recordings were made from single ganglion cells using methods described previously (Stapelfeldt & Szurszewski, 1989). Slow excitatory postsynaptic potentials (slow EPSPs) were evoked by repetitive stimulation of the lumbar colonic nerve.…”

“…When a ganglion was used for both electrophysiological and radioimmunological experiments, neurotensin8 13 (Sigma Chemicals, St Louis, MO, USA) was used instead of neurotensin113. It has been shown that neurotensin8'-3 causes similar electrophysiological changes to neurotensin1-'3 (Stapelfeldt & Szurszewski, 1989). Neurotensin8-'3 was used so as to avoid any possible interference with the radioimmunoassay for substance P. Although unlikely because of the duration of the experiments, it was nevertheless possible that some of the exogenously added peptide may not have been completely washed out of the preparation or completely degraded by the time a ganglion was removed from the bath and frozen.…”

“…Electrophysiological studies have shown that neurotensin increases the excitability of sympathetic neurones by a direct action on the postsynaptic membrane and predominantly by an indirect action on presynaptic nerve terminals to release a noncholinergic excitatory neurotransmitter (Stapelfeldt & Szurszewski, 1989). Substance P-, vasoactive intestinal polypeptide-, cholecystokinin-and bombesin-like materials are possible candidates mediating the indirect response to neurotensin.…”

Neurotensin excitation of rat ventral tegmental neurones.

“…This decrease in conductance results from a closure of potassium channels because in these cells the neurotensininduced current reversed polarity with strong hyperpolarization, and this reversal potential depended on the extracellular potassium concentration. An input resistant increase associated with the depolarization evoked by neurotensin has also been observed in rat frontal cortex pyramidal neurones (Audinat et al 1989), guinea-pig sympathetic ganglian neurones (Stapelfeldt & Szurszewski, 1989) and guinea-pig myenteric neurones (Williams et at. 1979).…”