Neuromedin-N inhibits migrating myoelectric complex and induces irregular spiking in the small intestine of rats; comparison with neurotensin

Abstract

The effects of neuromedin-N on migrating myoelectric complexes in the small intestine of rats were studied. As neuromedin-N and neurotensin are structurally related peptides a comparison with neurotensin was made. Myoelectric activity was recorded by means of three bipolar electrodes implanted into the wall of the small intestine at 5, 15 and 25 cm distal to the pylorus. The peptides were administered as intravenous infusions to fasted conscious rats. Neuromedin-N at doses of 100–800 pmol kg −1 min −1 caused a dose-dependent disruption of the migrating myoelectric complexes and induced irregular spiking activity ( n = 7, P < 0.05). Neurotensin induced a similar response, but at doses of 1.0–8.0 pmol kg −1 min −1 ( n = 5, P < 0.05). Thus, on a molar basis, neuromedin-N appeared to be about 100-times less potent than neurotensin. Hexamethonium (20 mg kg −1 i.v.) inhibited the migrating motor complexes and induced quiescence, but did not block the effect of neuromedin-N at a dose of 800 pmol kg −1 min −1. Atropine (1 mg kg −1 i.v.) and mepyramine (2 mg kg −1 i.v.) did not affect the migrating motor complexes, nor did they block the effect of neuromedin-N. Simultaneous infusion of neuromedin-N and neurotensin in a 1 : 1 molar ratio at doses of 2 pmol kg −1 min −1 showed inhibition of the response to neurotensin in eight out of ten experiments. In conclusion, neuromedin-N changes the myoelectric activity in the small intestine from a fasting to a fed pattern. Neuromedin-N is less potent but exerts similar effects as neurotensin. The mechanism of neuromedin-N action on motility could not be shown to involve cholinergic mechanisms or H 1-receptors, but may involve the same receptors as neurotensin, modulating the effects of this peptide.