“…In the gastrointestinal tract, galanin is localized to nerve cell bodies in both myenteric and submucosal plexuses and neuronal processes projecting to the smooth muscle and mucosa (Ekblad et al, 1985b; Furness et al, 1987). The regional and cellular distribution of galanin is consistent with its involvement in the regulation of neurotransmitter and hormone release, acid secretion, motility, and ion transport (Ekblad et al, 1985a; McCulloch et al, 1987; Bauer et al, 1989; Homaidan et al, 1994; Kisfalvi et al, 2000).…”
Galanin activates three receptors, the galanin receptor 1 (GalR1), GalR2 and GalR3. In the gastrointestinal tract, GalR1 mediates the galanin inhibition of cholinergic transmission to the longitudinal muscle and reduction of peristalsis efficiency in the small intestine. Galanin has also been shown to inhibit depolarization-evoked Ca 2+ increases in cultured myenteric neurons. Since GalR1 immunoreactivity is localized to cholinergic myenteric neurons, we hypothesized that this inhibitory action of galanin on myenteric neurons is mediated by GalR1. We investigated the effect of galanin 1-16, which has high affinity for GalR1 and GalR2, in the presence or absence of the selective GalR1 antagonist, RWJ-57408, and of galanin 2-11, which has high affinity for GalR2 and GalR3, on Ca 2+ influx through voltage-dependent Ca 2+ channels in cultured myenteric neurons. Myenteric neurons were loaded with fluo-4 and depolarized by high K + concentration to activate voltage-dependent Ca 2+ channels. Intracellular Ca 2+ levels were quantified with confocal microscopy. Galanin 1-16 (0.01-1 µM) inhibited the depolarization-evoked Ca 2+ increase in a dose-dependent manner with an EC 50 of 0.172 µM. The selective GalR1 antagonist, RWJ-57408 (10 µM) blocked the galanin 1-16 (1µM) mediated inhibition of voltage-dependent Ca 2+ channel. By contrast, the GalR2/GalR3 agonist, galanin 2-11 did not affect the K + -evoked Ca 2+ influx in myenteric neurons. GalR1 immunoreactivity was localized solely to myenteric neurons in culture as previously observed in intact tissue. These findings indicate that the inhibition of depolarization-evoked Ca 2+ influx in myenteric neurons in culture is mediated by GalR1 and confirm the presence of functional GalR1 in the myenteric plexus. This is consonant with the hypothesis that GalR1 mediates galanin inhibition of transmitter release from myenteric neurons.
“…In the gastrointestinal tract, galanin is localized to nerve cell bodies in both myenteric and submucosal plexuses and neuronal processes projecting to the smooth muscle and mucosa (Ekblad et al, 1985b; Furness et al, 1987). The regional and cellular distribution of galanin is consistent with its involvement in the regulation of neurotransmitter and hormone release, acid secretion, motility, and ion transport (Ekblad et al, 1985a; McCulloch et al, 1987; Bauer et al, 1989; Homaidan et al, 1994; Kisfalvi et al, 2000).…”
Galanin activates three receptors, the galanin receptor 1 (GalR1), GalR2 and GalR3. In the gastrointestinal tract, GalR1 mediates the galanin inhibition of cholinergic transmission to the longitudinal muscle and reduction of peristalsis efficiency in the small intestine. Galanin has also been shown to inhibit depolarization-evoked Ca 2+ increases in cultured myenteric neurons. Since GalR1 immunoreactivity is localized to cholinergic myenteric neurons, we hypothesized that this inhibitory action of galanin on myenteric neurons is mediated by GalR1. We investigated the effect of galanin 1-16, which has high affinity for GalR1 and GalR2, in the presence or absence of the selective GalR1 antagonist, RWJ-57408, and of galanin 2-11, which has high affinity for GalR2 and GalR3, on Ca 2+ influx through voltage-dependent Ca 2+ channels in cultured myenteric neurons. Myenteric neurons were loaded with fluo-4 and depolarized by high K + concentration to activate voltage-dependent Ca 2+ channels. Intracellular Ca 2+ levels were quantified with confocal microscopy. Galanin 1-16 (0.01-1 µM) inhibited the depolarization-evoked Ca 2+ increase in a dose-dependent manner with an EC 50 of 0.172 µM. The selective GalR1 antagonist, RWJ-57408 (10 µM) blocked the galanin 1-16 (1µM) mediated inhibition of voltage-dependent Ca 2+ channel. By contrast, the GalR2/GalR3 agonist, galanin 2-11 did not affect the K + -evoked Ca 2+ influx in myenteric neurons. GalR1 immunoreactivity was localized solely to myenteric neurons in culture as previously observed in intact tissue. These findings indicate that the inhibition of depolarization-evoked Ca 2+ influx in myenteric neurons in culture is mediated by GalR1 and confirm the presence of functional GalR1 in the myenteric plexus. This is consonant with the hypothesis that GalR1 mediates galanin inhibition of transmitter release from myenteric neurons.
“…The approach taken in the present study, in which jejunal contraction can be compared to the pharmacological profile of each individual receptor subtype expressed in CHO and COS‐7 cells (Table 1), allows a clearer correlation to emerge. Human GalR1 receptor has been isolated from mucosal cells lining the human gastrointestinal tract by RT‐PCR using human GalR1‐specific primers [21], suggesting a role for galanin in regulation of intestinal epithelial cell absorption [39]. In the present study, we extended to measure the relative amounts of all the three GalR subtypes in rat jejunum by Northern blot analysis.…”
The neuropeptide galanin mediates a diverse array of physiological functions through activation of specific receptors. Roles of the three recently cloned galanin receptors (GalRs) in rat intestinal contraction and food intake were examined using GalR-selective ligands and the results were compared with the pharmacological profiles of defined GalRs. The action profile of these ligands in jejunal contraction resembled only that of GalR2 and only a high level of GalR2 mRNA was detected in the tissue, supporting GalR2 as the receptor mediating jejunal contraction. The action profile for food intake in rats excluded GalR2, GalR3 and the putative pituitary galanin receptor as the`feeding receptor', suggesting that either GalR1 or an unidentified GalR is responsible for mediating this function.z 1998 Federation of European Biochemical Societies.
“…Within the small intestine, galanin alone decreased Isc and thus net ion secretion in pig jejunum 7 and rabbit ileum. 8 In contrast, galanin had no effect on basal Isc in rat jejunum. 9 Whereas galanin had no effect on basal Isc in guinea pig colon, 10 this peptide caused a massive and prolonged increase in net electrogenic ion secretion in rat colon.…”
Section: Galanin‐1 Receptor Expression and Function In Epithelial Celmentioning
Galanin is widely distributed in enteric nerves and nerve terminals throughout the gastrointestinal (GI) tract. Within the GI tract galanin is best known for its ability to alter smooth muscle contractility and regulate intestinal motility. However, recent studies also indicate that galanin can modulate epithelial ion transport. We previously showed that epithelial cells lining the human GI tract, including those of colonic origin, express Gal1 galanin receptors (Gal1-R). We herein demonstrate that epithelial cells lining the human colon only express Gal1-R receptors and do not express other galanin receptor subtypes. We previously showed that Gal1-R expression was transcriptionally regulated by the transcription factor NF-kappa B. Consistent with this transcription factor being activated in a number of inflammatory conditions, we show increased colonic Gal1-R expression in patients with colitis due to a variety of causes. To further evaluate the physiology of Gal1-R activation, we studied this receptor expressed by the human colon epithelial cell line T84. Gal1-R activation resulted in a dose-dependent increase in Cl- secretion; whereas infection of T84 cells with pathogens known to activate NF-kappa B augmented Gal1-R expression and Cl- secretion. Thus, galanin acts as a secretagogue in epithelial cells lining the human colon, with alterations in Gal1-R expression possibly playing an important role in the diarrhea associated with various inflammatory processes affecting the GI tract.
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