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

Abstract

It has been shown in cats that gastric motor control by the dorsal vagal complex and nucleus ambiguus is under a tonic GABAergic influence. Since much more work has been performed in rats to define vago-vagal reflexes controlling gastrointestinal function, an understanding of the potential inhibition by candidate neurotransmitters such as GABA (gamma aminobutyric acid) in the rat dorsal vagal complex (DVC) is essential to assess. Multiple-barrelled micropipettes were used to apply to the dorsal vagal complex the GABAA antagonist, bicuculline methiodide (0.1-1 nmol), and a GABAA agonist, muscimol (10 nmol) prior to micro-injection of the GABAA antagonist. Micro-injections of bicuculline (353 pmol and 1 nmol), which were localized primarily in the dorsal motor nucleus of the vagus, produced significant increases in intragastric pressure and pyloric motility. These responses were abolished by vagotomy and by a prior micro-injection of muscimol. To determine whether GABAergic blockade in the dorsal vagal complex results in gastric motor excitation through excitatory amino acid receptors, kynurenic acid (5 nmol), a kainate/NMDA (N-methyl D-aspartic acid) receptor antagonist, was micro-injected prior to bicuculline. This abolished the increase in gastric motor function normally evoked by bicuculline. In the other two important hindbrain nuclei controlling gastric function, the nucleus raphe obscurus and nucleus ambiguus, bicuculline (353 pmol) significantly increased intragastric pressure via vagally mediated pathways. These data demonstrate that all three rat hindbrain nuclei known to influence gastric function via the vagus nerve are under tonic GABAergic control. In addition, in the dorsal vagal complex, relief from GABAergic inhibition results in increases in gastric motor function through kainate/NMDA receptor-mediated excitation.

Excitatory and inhibitory local circuit input to the rat dorsal motor nucleus of the vagus originating from the nucleus tractus solitarius

“…Although most have focused on an inhibitory connection, [11,18,25,32] the existence of an excitatory connection has also been suggested [5,32]. Anatomical evidence for the existence of a direct connection between the NTS and DMV is based primarily on dye injections into the NTS [23], retrograde transneuronal viral labeling of NTS neurons after infection of terminal fields in the viscera [6,12], ormorphological identification of neurons known to project to DMV [12].…”

Effect of antipyrine on the gastric emptying of liquid in rats

“…The activation of GABA B receptors by baclofen in the CNS results in hyperpolarization of the postsynaptic membranes or in inhibition of neurotransmitter release at presynaptic nerve endings (19,20). There is strong evidence that GABA, through GABA B receptors, may participate in the control of gastric secretion and gastrointestinal motility at the level of the nucleus tractus solitarii (19,(21)(22)(23)(24)(25)(26). On this basis, we may speculate that the stimulation of presynaptic GABA B receptors by baclofen, by blocking the excitation of the non-adrenergic cholinergic (inhibitory) pathway and/or the inhibition of the cholinergic (stimulatory) pathway of the vagus determined by antipyrine, may explain the results of the present study.…”

Effect of 4-aminoantipyrine on gastric compliance and liquid emptying in rats

“…In the CNS, bac activates GABA B receptors, promoting modulation of neurotransmission by hyperpolarization of the postsynaptic membranes or inhibition of neurotransmitter release at the presynaptic endings (18). There is evidence that GABA participates in the control of gastric motility at the level of the nucleus tractus solitarii, a CNS structure that receives afferent information through the vagus nerve (19)(20)(21).…”