Mechanisms of neurotensin-induced inhibition in rat ileal smooth muscle
Allescher, H.D.; Fick, H.; Schusdziarra, V.; Classen, M.
American Journal of Physiology 263(5 Pt 1): G767-G774
1992
ISSN/ISBN: 0002-9513 PMID: 1279984 Document Number: 389945
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 (IC-50): 2.8 times 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 times 10-5 M), 4-aminopyridine (10-4 M to 5 times 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 (IC-50: 2.4 times 10-9 M) or verapamil (IC-50: 1.1 times 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 Ca-2+ stores by repetitive stimulation with CCH and caffeine in Ca-2+-free buffer, reintroduction of external Ca-2+ 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. These results suggest that neurotensin opens an apamin-sensitive, possibly Ca-2+-activated K+ channel and thus causes an inhibition of ileal smooth muscle contractions.