Role of galanin receptor 1 in gastric motility in rat

Abstract

Galanin actions are mediated by distinct galanin receptors (GAL-R), GAL-R1, -R2 and -R3. We investigated the role of GAL-R1 in gastric motility and the expression of GAL-R1 in the rat stomach. In vivo, in urethane-anaesthetized rats, galanin (equipotent for all GAL-Rs) induced a short inhibition of gastric motility, followed by increase in tonic and phasic gastric motility; the latter was significantly reduced by the GAL-R1 antagonist, RWJ-57408. Galanin 1-16 (high affinity for GAL-R1 and -R2) induced a long-lasting decrease of intragastric pressure, which was not modified by RWJ-57408. In vitro, galanin and galanin 1-16 induced increase of intragastric pressure that was not affected by RWJ-57408. Tetrodotoxin (TTX) did not suppress the galanin excitatory effect, whereas the effect of galanin 1-16 on gastric contraction was increased by TTX- or N-nitro-L-arginine, an inhibitor of nitric oxide synthase. GAL-R1 immunoreactivity was localized to cholinergic and tachykinergic neurons and to neurons immunoreactive for nitric oxide synthase or vasoactive intestinal polypeptide. This study suggests that an extrinsic GAL-R1 pathway mediates the galanin excitatory action, whereas an extrinsic, non GAL-R1 pathway is likely to mediate the galanin inhibitory effect in vivo. GAL-R1 intrinsic neurons do not appear to play a major role in the control of gastric motility.

Expression of galanin receptor messenger RNAs in different regions of the rat gastrointestinal tract

“…In contrast, in vitro, galanin has only an excitatory, tetrodotoxin-independent effect, indicating a nonneuronal, direct effect on smooth muscle. This effect is likely to be mediated by GalR2 [10], the only GalR that signals through a stimulatory Gq/11 pathway, thus its activation by galanin could result in smooth muscle contraction [6]. Participation of GalR2 in the effect of galanin on gastric motility is supported by our findings of high levels of GalR2 mRNA in the stomach and is consistent with functional studies indicating the GalR2 as the main GalR implicated in the excitatory mechanism for smooth muscle contraction [27].…”

The Influence of Gastric Antral Ulcerations on the Expression of Galanin and GalR1, GalR2, GalR3 Receptors in the Pylorus with Regard to Gastric Intrinsic Innervation of the Pyloric Sphincter

“…Considering the gastrointestinal tract, GalR1 is mainly expressed by extrinsic [ 31 ; 80 ] and intramural [ 6 ; 30 ; 32 ; 81 – 84 ] neurons as well as by enterochromaffin-like and epithelial cells [ 84 ; 85 ]. The GalR1 is suggested to facilitate galanin actions on gastrointestinal functions (such as motility and secretion) mainly by modulation of other neurotransmitters release [ 86 ].…”

“…This receptor has been proposed to mediate many inhibitory actions of galanin [ 80 ; 87 ]. GalR1 pathways are strongly involved in the gastric [ 31 ] and jejunal [ 32 ] motility regulation. The expression of GalR1has been found to be upregulated in peripheral tissues in almost all experimental inflammatory models [ 1 ], what is in agreement with results obtained in our study.…”

Modulation of gastric motility by brain-gut peptides using a novel non-invasive miniaturized pressure transducer method in anesthetized rodents

“…Collectively the data obtained in rats using prokinetic peptides such as iv ghrelin and central vagal cholinergic activation in fasted urethane anesthetized rats validate the sensitivity and reliability of the novel non surgical acute method with pressure microsensor catheter inserted orally. Of note is that urethane anesthesia was used to conduct the validation of the non-invasive method for comparison purpose to a number of reports showing that iv injection of ghrelin or central vagal activation stimulates high amplitude phasic contractions monitored by different recording approaches in urethane anesthetized rats [1,9,27,40,55,55]. In addition, the stimulation induced by central vagal activation and ghrelin or other transmitters initially observed in urethane anesthetized rats have been largely reproduced in conscious rats [18,21,63,64].…”

“…In addition, the stimulation induced by central vagal activation and ghrelin or other transmitters initially observed in urethane anesthetized rats have been largely reproduced in conscious rats [18,21,63,64]. However urethane results in the activation of sympathetic outflow [8], hyperglycemia [27] and gastric somatostatin release [71] that can impact on gastric motor function [51]. Therefore it will be relevant to expand this non-invasive pressure microsensor method under other anesthetic conditions (inactin, pentobarbital) also used to record gastric motility.…”