Mechanisms of neurotensin-induced inhibition in rat ileal smooth muscle

H. D. Allescher, H. Fick, V. Schusdziarra, M. Classen

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The aim of the present study was to determine the mechanisms of neurotensin-induced inhibition in ileal smooth muscle. Isolated rat ileal smooth muscle strips were stimulated in an organ bath using carbachol (CCH) or by KCl depolarization. Neurotensin produced a concentration-dependent inhibition of muscle contraction [mean inhibitory concentration (IC50): 2.8 x 10-9 M], which was not blocked by phentolamine (10-6 M), hexamethonium (10-4 M), indomethacin (10-6 M), nordihydroguaretic acid (10-6 M), or tetrodotoxin (10-6 M). The inhibitory effect of neurotensin during CCH stimulation was blocked concentration dependently in the presence of the K+- channel blocker apamin. By contrast, other K+-channel blockers such as 9- aminoacridine (10-6 M to 3 x 10-5 M), 4-aminopyridine (10-4 M to 5 x 10-3 M), tetraethylammonium (10-4 M to 10-1 M), or glibenclamide (10- 5 M) were ineffective. The presence of the Ca2+-channel antagonist nitrendipine (IC50:2.4 x 10-9 M) or verapamil (IC50: 1.1 x 10-7 M) also blocked the neurotensin inhibitory effect. Ileal contraction, induced by the Ca2+-channel activator BAY K 8644 (10-7 M), was completely inhibited by neurotensin. After depletion of internal Ca2+ stores by repetitive stimulation with CCH and caffeine in Ca2+-free buffer, reintroduction of external Ca2+ restored neurotensin inhibition of the contraction induced by CCH. These results demonstrate that the inhibitory effect of neurotensin in rat ileum longitudinal muscle is apamin sensitive and cannot be observed in the presence of the Ca2+-channel blockers nitrendipine or verapamil. These results suggest that neurotensin opens an apamin-sensitive, possibly Ca2+- activated K+ channel and thus causes an inhibition of ileal smooth muscle contractions.

Original languageEnglish
Pages (from-to)G767-G774
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume263
Issue number5 26-5
DOIs
StatePublished - 1992

Keywords

  • apamin
  • calcium ion-channel blockers
  • potassium-channel blockers

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