CONCENTRATION-DEPENDENT STIMULATION OF CHOLINERGIC MOTOR NERVES OR SMOOTH-MUSCLE BY [NLE(13)]MOTILIN IN THE ISOLATED RABBIT GASTRIC ANTRUM

In man, rabbit and cat, the effects of motilin and motilides are neura lly mediated in vivo, whereas in vitro binding and contractility studi es suggest the presence of a smooth muscular receptor. The aim of this study was to investigate in vitro interactions of motilin with the en teric excitatory neurotransmission in the gastric antrum of the rabbit . Circular muscle strips from the pre-pyloric antrum were subjected to electrical field stimulation (1 ms, 1-32 Hz, 10 s train) and muscle t witch responses were recorded isometrically. Induced twitch responses were frequency dependent (1-32 Hz) and entirely neurogenic (tetrodotox in sensitive). [Nle(13)]motilin dose-dependently (10(-9)-10(-8) M) enh anced the amplitude of, atropine sensitive, evoked contractions. At 4 Hz the response, expressed as a % of the response to 32 Hz, increased from 15.5 +/- 4.1% (control) to 28.1 +/- 5.8% (motiiin 10(-9) M), and to 45.8 +/- 3.6% (motilin 10(-8.5) M) (P < 0.05). This effect was not inhibited by hexamethonium (10(-3.3) M) but was abolished by the motil in receptor antagonist GM-109 (10(-5) M). In unstimulated strips, moti lin induced phasic-tonic contractions with a threshold concentration o f 10(-8) M and an pEC(50) of 7.48, which were also inhibited by GM-109 (10(-5) M) but not by tetrodotoxin (10(-5.5) M). The maximal tension, frequency and dose-dependency of carbachol-induced contractions were not influenced by motilin (pEC(50), carbachol: 6.48 +/- 0.06 (control) , 6.49 +/- 0.07 (motilin)). In conclusion, motilin enhances contractio ns induced by electrical field stimulation in the rabbit antrum by a p ost-ganglionic interaction with the cholinergic neurotransmission in v itro at low doses and interacts directly with antral smooth muscle at high doses. This model is an accurate reflection of the in vivo effect s of motilin and provides a tool to study neurogenic and myogenic acti ons of motilin and motilides in vitro. (C) 1997 Elsevier Science B.V.