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Am J Physiol Gastrointest Liver Physiol 263: G767-G774, 1992;
0193-1857/92 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 263, Issue 5 767-G774, Copyright © 1992 by American Physiological Society

ARTICLES

Mechanisms of neurotensin-induced inhibition in rat ileal smooth muscle

H. D. Allescher, H. Fick, V. Schusdziarra and M. Classen
Department of Internal Medicine II, Technical University of Munich, Federal Republic of Germany.

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 Ca(2+)-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 Ca(2+)-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 Ca(2+)-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 Ca(2+)-channel blockers nitrendipine or verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)


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