Neurotensin: a modulator of enteric cholinergic neurons in the guinea pig small intestine.

Release of [3H]acetylcholine was studied in the presence of neurotensin (NT) on the myenteric plexus-longitudinal muscle strips (MPLM) from the guinea pig small intestine. In the dose range from 3 pM to 3 nM, NT induced a dose-related increase in the efflux of [3H]acetylcholine from the MPLM. This release was completely inhibited by 1.5 X 10(-6) M tetrodotoxin. The output of acetylcholine evoked by NT (7.5 X 10(-11) M) was significantly depressed by the addition of somatostatin (6.1 X 10(-7) M) or methionine-enkephalin (8.7 X 10(-8) M). Release of newly synthesized [3H]acetylcholine from the isolated synaptic terminals (synaptosomes) was also examined in the presence of NT (1.5 X 10(-7) M) or 20 mM KCl. Release of [3H]acetylcholine was significantly elevated by either stimulants. It was concluded that neurotensin stimulated ACh release via a neurogenic mechanism, probably by a presynaptic site of action on myenteric cholinergic neurons. Despite a paucity of NT-containing neurons in the myenteric plexus, results from this study support a neuromodulatory role for NT in the regulation of local cholinergic neuronal activity in the gut.