Gastric effects of TRH analogue and bicuculline injected into dorsal motor vagal nucleus in cats

Abstract

We investigated the gastric acid secretory and motility responses to microinjection into the dorsal motor nucleus of the vagus (DMV) of RX 77368, a stable thyrotropin-releasing hormone (TRH) analogue, and bicuculline, a gamma-aminobutyric acid (GABAA) receptor antagonist in ketamine-chloralose-anesthetized cats. Gastric acid output was collected every 15 min through a gastric cannula after saline flush and titrated to pH 7.0. Antral contractions were continuously recorded by an extraluminal strain gauge force transducer. The chemicals were dissolved in saline and unilaterally microinjected in volumes of 200 nl. RX 77368 or bicuculline microinjected into the DMV induced significant dose-dependent (50-500 ng) increases in gastric acid secretion and significant dose-dependent (50-200 ng) increases in the force of antral contractions. In response to both chemicals the gastric acid output increased in the first 15 min and peaked in the second and third collections. RX 77368 (500 ng) had a second greater peak 90 min after microinjection. The motility responses were rapid in onset and lasted 60 min for RX 77368 and 30 min for bicuculline. The minimal effective dose for eliciting increased motility was consistently lower than inducing acid secretion. Electrical stimulation of the DMV with 100 microA, 50-Hz, and 0.2-ms pulse duration increased the force of antral contractions but had no effect on gastric acid secretion. Our results demonstrate that the DMV exerts important control over both gastric acid secretion and motility in cats. TRH exerts a stimulatory influence, while GABAA receptors mediate an inhibitory influence on this vagal control.

Role of GABAA receptors in rat hindbrain nuclei controlling gastric motor function

“…An early study found that micro‐injection of BMI into the DMV of cats, at a dose of ≈200 pmol, did not result in any gastric motility alterations 18 . However, subsequent reports have shown that BMI at this site dose‐dependently increases gastric acid secretion and antral contractility 9 , 10 and alters lower oesophageal sphincter pressure 10 . In the present study in rats, BMI (353 pmol) micro‐injected into the DMV, significantly increased IGP and pyloric motility, while the highest dose of BMI (1 nmol) significantly increased all indices of gastric motor function recorded.…”

“…However, to date, functional GI studies on GABAergic transmission in the DVC have only been performed in felines. In cats, micro‐injection of a GABA A antagonist, bicuculline methiodide (BMI) into the DMV produces dose‐dependent increases in gastric contractile activity and secretion 9 . 10 While electrophysiological studies in rats support the notion that neurones of the DMV receive a GABAergic inhibitory input, 8 , 11 it is not known whether GABA A receptors play a role in extrinsic control of gastric motor function in rodents.…”

Diabetes induces GABA receptor plasticity in murine vagal motor neurons

“…Inhibitory, GABAergic neurotransmission is arguably the most prominent regulator of ongoing vagal motorneuron activity (Travagli et al 2006). GABA A receptor antagonist application into the vagal complex significantly alters gastrointestinal and pancreatic function (Feng et al 1990;Mussa and Verberne 2008;Washabau et al 1995). Vagally mediated visceral functions related to energy homeostasis are thus tightly regulated by GABAergic signaling in the vagal complex.…”

Differential organization of excitatory and inhibitory synapses within the rat dorsal vagal complex

“…More specifically, a series of studies focused on the GI responses to microinjections of the GABA-and glutamaterelated substances in the brain stem. Microinjections of the specific GABA A antagonist bicuculline methiodide (BIC) into the DMV increase gastric acid secretion, intragastric pressure, and exocrine pancreatic secretions (27,44,53), suggesting that DMV neurons innervating the stomach and the exocrine pancreas receive tonic GABAergic inputs. Glutamate, in contrast, appears to exert site-specific effects on esophageal and gastric motility.…”