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

W. H. Stapelfeldt, J. H. Szurszewski

Research output: Contribution to journalArticle

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Abstract

Intracellular, electrophysiological techniques were combined with radioimmunological, chromatographic and pharmacological techniques to determine if nerve terminals containing substance P mediated transient depolarizing responses of principal ganglion cells induced by neurotensin. Experiments were performed in vitro on guinea-pig inferior mesenteric ganglia. In 61% of principal ganglion cells tested in normal ganglia, neurotensin8-13 caused a transient membrane depolarization. In ganglia which were removed from animals which had been pre-treated with capsaicin, transient responses to neurotensin were virtually abolished. In normal ganglia, neurotensin8-13 increased the amplitude and duration of non-cholinergic slow EPSPs evoked by electrical stimulation of the lumbar colonic nerve. Such increases were absent in ganglia obtained from animals pre-treated with capsaicin. In guinea-pigs pre-treated with capsaicin, the content of substance P-like material was significantly reduced in inferior mesenteric and coeliac ganglia, dorsal root ganglia and lumbar spinal cord, compared to control animals. The content of substance P-like material in segments of distal colon was slightly reduced. The content of vasoactive intestinal polypeptide-, cholecystokinin- and bombesin-like material in the same tissues from animals pre-treated with capsaicin was not significantly different from control animals. Chromatographic analysis using HPLC (high-performance liquid chromatography) techniques revealed that the material depleted from inferior mesenteric and coeliac ganglia, dorsal root ganglia and lumbar spinal cord by capsaicin pretreatment co-eluted with synthetic substance P. Electrical stimulation of the lumbar colonic nerve released substance P-like material from isolated inferior mesenteric ganglia as determined by radioimmunoassay of samples of superfusate. Exogenous administration of neurotensin8-13 caused a significant increase in the amount of substance P-like material released during nerve stimulation. Transient depolarizing responses evoked by neurotensin were markedly attenuated when ganglion cells were postsynaptically desensitized to exogenously administered substance P. Taken together, these findings suggest that transient depolarizations mediated by an indirect action of neurotensin and facilitation of electrically evoked non-cholinergic slow EPSPs by neurotensin involved presynaptic release of substance P from collateral nerve terminals of primary afferent nerve fibres in the inferior mesenteric ganglion. It was suggested that under normal in vivo conditions, neurotensin or a C-terminal-related peptide contained in central preganglionic nerve endings might function as an excitatory neuromodulator to enhance the release of substance P from primary afferent nerve terminals thereby facilitating non-cholinergic peripheral afferent synaptic input to prevertebral ganglion cells.

Original languageEnglish (US)
Pages (from-to)325-345
Number of pages21
JournalJournal of Physiology
Volume411
StatePublished - 1989

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Neurotensin
Substance P
Ganglia
Guinea Pigs
Capsaicin
Spinal Cord
Sympathetic Ganglia
Excitatory Postsynaptic Potentials
Spinal Ganglia
Electric Stimulation
Bombesin
Nerve Endings
Vasoactive Intestinal Peptide
Cholecystokinin
Nerve Fibers
Radioimmunoassay
Neurotransmitter Agents
Chromatography
Colon
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Physiology

Cite this

Neurotensin-facilitates release of substance P in the guinea-pig inferior mesenteric ganglion. / Stapelfeldt, W. H.; Szurszewski, J. H.

In: Journal of Physiology, Vol. 411, 1989, p. 325-345.

Research output: Contribution to journalArticle

Stapelfeldt, W. H. ; Szurszewski, J. H. / Neurotensin-facilitates release of substance P in the guinea-pig inferior mesenteric ganglion. In: Journal of Physiology. 1989 ; Vol. 411. pp. 325-345.
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