ABSTRACT
The study aims to find the effect of motilin on neuronal activity of gastric distension-responsive neurons in rat hippocampus and its possible mechanism. Single unit discharges in the hippocampal CA1 region were recorded extracellularly by means of four-barrel glass micropipettes in anesthetized rats and the expression of nNOS in hippocampus was observed by fluo-immunohistochemistry staining. Of the 171 recorded neurons, 76.0% were GD-excitatory (GD-E) neurons and 24.0% were GD-inhibited (GD-I) neurons. The 57.6% of GD-E neurons showed an excitatory response to motilin and the same effect was observed in 51.7% GD-I neurons. However, when NOS inhibitor nitro-l-arginine methyl ester (l-NAME) was administrated previously, the followed motilin-induced excitatory responsiveness of GD-responsive neurons was reduced. In contrast, discharge activity of GD-responsive neurons with motilin was enhanced by pretreatment of NO precursor l-arginine. The expression of nNOS-IR positive neurons was significantly increased in CA1 after administration of motilin. Our findings suggested that motilin excited the GD-responsive neurons in the hippocampal CA1 region and the excitatory effect of motilin may be mediated by the endogenous NO.
Subject(s)
Gastrointestinal Agents/pharmacology , Hippocampus/physiology , Motilin/pharmacology , Neurons/physiology , Action Potentials/drug effects , Animals , Gastric Dilatation/etiology , Gastrointestinal Agents/administration & dosage , Hippocampus/drug effects , Hippocampus/metabolism , Male , Motilin/administration & dosage , NG-Nitroarginine Methyl Ester/administration & dosage , NG-Nitroarginine Methyl Ester/pharmacology , Neurons/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/antagonists & inhibitors , Nitric Oxide Synthase Type I/metabolism , Rats , Rats, WistarABSTRACT
Motilin and motilin receptors have been found in most regions of the brain, including the amygdala, one of the most important parts of the limbic system. Our previous study found that administration of motilin in the hippocampus stimulates gastric motility. We now explore the effect of motilin in the amygdala on gastric motility. In conscious rats, gastric motility was recorded after microinjection of motilin, motilin receptor antagonist (GM-109) or a mixture of the two into the basomedial amygdala nucleus (BMA). In anesthetized rats the changes of spontaneous discharges of gastric distention sensitive neurons (GDSN) in the BMA were recorded after intracerebroventricular (i.c.v.) microinjection of motilin or GM-109. In conscious rats the amplitude of gastric contractions increased dose-dependently after microinjection of motilin in the BMA, and decreased after microinjection of GM-109. The excitatory or inhibitory effects induced by motilin or GM-109 alone, were weakened by microinjection of a mixture solution of both. The spontaneous discharge frequency of gastric distention excitatory neuron (GDEN) was mainly inhibited by i.c.v. microinjection of motilin but excited by GM-109. In contrast, the spontaneous discharge frequency of gastric distention inhibitory neuron (GDIN) was mainly excited by motilin, but inhibited by GM-109. Our findings suggest that motilin may regulate gastric motility by modulating neural pathways in the BMA.
Subject(s)
Amygdala/drug effects , Gastrointestinal Motility/drug effects , Motilin/pharmacology , Amygdala/cytology , Amygdala/physiology , Animals , Electrophysiology , Female , Injections, Intraventricular , Male , Microinjections , Motilin/administration & dosage , Neurons/drug effects , Peptides, Cyclic/administration & dosage , Peptides, Cyclic/pharmacology , Rats , Receptors, Gastrointestinal Hormone/antagonists & inhibitors , Receptors, Neuropeptide/antagonists & inhibitorsABSTRACT
Ghrelin was first discovered as a peptide involved in growth hormone release, but has now emerged as a new player in the regulation of gastrointestinal function. Ghrelin is structurally and functionally related to motilin. Like motilin, it induces a specific motor pattern in the fasted state and acts postprandially to accelerate gastric emptying. There is no apparent cross-reactivity with motilin at the receptor level. Ghrelin agonists have the same potential as motilin agonists, and applications in post-operative ileus and gastroparesis have already been explored. Although promising, there is still the need to avoid side effects and the problems encountered with motilides. This will require drugs with an appropriate pharmacokinetic profile. In addition, the dosage regimen and target population should be carefully taken into consideration when planning clinical trials.
