Disease relevance of Galr1

• GALR1 activity is linked to a pertussis toxin (PTX)-sensitive opening of G protein-gated K+ channels (GIRKs) [1].
• Cloning and characterization of the rat GALR1 galanin receptor from Rin14B insulinoma cells [2].
• When the rats were water deprived for 2 days the presynaptic response to GAL was unaltered; however, the postsynaptic decrease in input resistance and hyperpolarization was increased, an effect consistent with a previously described increase in GAL1 receptor expression in dehydration [3].
• Antinociceptive effects of galanin in the rat tuberomammillary nucleus and the plasticity of galanin receptor 1 during hyperalgesia [4].
• These effects were observed in 21 of the 33 dorsal root ganglion neurones studied and were not attenuated by the galanin receptor antagonist galantide [5].

Psychiatry related information on Galr1

• Activity of centrally administered galanin fragments on stimulation of feeding behavior and on galanin receptor binding in the rat hypothalamus [6].
• The results clearly support the hypothesis that neuropeptides such as GAL are an integral component of the neural response to psychological stress, although the functional significance of the changes in GAL receptor density described in this study awaits elucidation [7].
• Nonpeptide, bioavailable, subtype-selective galanin receptor antagonists may provide tools to test the hypothesis that antagonism of endogenous galanin, which is overexpressed in the basal forebrain in Alzheimer's patients, can contribute to the alleviation of the cognitive deficits associated with Alzheimer's disease [8].

High impact information on Galr1

• Direct activation of galanin receptors by a galanin receptor agonist, galnon, was found to produce an antidepressant-like effect in the same task [9].
• Furthermore, a galanin receptor antagonist, M40, attenuated the antidepressant-like effect of FLX in the forced swim test, a rodent preclinical screen commonly used to evaluate antidepressant-like efficacy [9].
• Several galanin receptor subtypes are present in dorsal root ganglia and spinal cord with a differential distribution [10].
• Also, GAL receptor-1 mRNA was expressed in the sensory ganglia of embryos but appeared later than the ligand [11].
• Galanin receptor-mediated inhibition of glutamate release in the arcuate nucleus of the hypothalamus [12].

Chemical compound and disease context of Galr1

• Systemic galnon, a low-molecular weight galanin receptor agonist, reduces heat hyperalgesia in rats with nerve injury [13].
• Finally, the expression of galanin message associated peptide (GMAP) mRNA in dorsal root ganglion (DRG) cells and the effects of the high affinity galanin receptor antagonist M35 on the flexor reflex in RTX-treated rats were evaluated [14].

Biological context of Galr1

• The GALR2 amino acid sequence is 38% identical to GALR1 and is pharmacologically similar to GALR1 when expressed in COS-7 cells [15].
• Because a portion of GAL receptors in this region have been postulated to function as presynaptic auto-receptors on cholinergic fiber terminals, the reduction in GAL binding sites with age may be a consequence of age-related alterations in GAL receptor expression by basal forebrain cholinergic neurons which project to the ventral hippocampus [16].
• It was not associated with a significant change in peak GALR1 gene expression in the hippocampus [16].
• These studies demonstrate these chimeric analogs will not be useful for defining the physiological role of galanin in altering gastrointestinal motility, because they function as full galanin-receptor agonists instead of as galanin-receptor antagonists [17].
• Cross-desensitization experiments demonstrated that in the jejunal muscle strips, both chimeric analogs were causing muscle contraction by interacting with the galanin receptor [17].

Anatomical context of Galr1

• GAL inhibition of midbrain DA activity may involve a GALR1- mediated reduction of TH in midbrain dopaminergic neurons [1].
• A possible role for the GAL-R1 receptor subtype in cognition in the dorsal and ventral hippocampus remains to be defined [18].
• We describe the cloning of a second galanin receptor type, GALR2, from rat hypothalamus [15].
• Subsequent studies revealed the presence of galanin receptor-1-like immunoreactivity (GALR1-LI) in most cell types shown to contain GAL-LI, although the distribution of GALR1-LI was more extensive in reserve zone chondrocytes than that of GAL-LI; and GALR1-LI also appeared in late proliferative zone chondrocytes of costal cartilage [19].
• Rat myometrium expresses GALR2 but not GALR1 mRNA [20].

Associations of Galr1 with chemical compounds

• Expression cloning of a rat hypothalamic galanin receptor coupled to phosphoinositide turnover [21].
• Expression of GalR1 and GalR2 galanin receptor messenger ribonucleic acid in proopiomelanocortin neurons of the rat arcuate nucleus: effect of testosterone [22].
• To evaluate the functional relevance of this anatomical relationship, the effects of intraventricular injection of a GAL receptor antagonist, galantide, were examined on NPY-induced LH release in ovarian steroid-primed ovariectomized rats [23].
• The present study aimed at investigating how a non-peptide galanin receptor agonist, galnon, affects insulin secretion from isolated pancreatic islets of healthy Wistar and diabetic Goto-Kakizaki (GK) rats [24].
• In contrast, we detected an extensive co-expression (95%) of GALR1 mRNA within extrahypothalamic VP/GAL neurons [25].

Regulatory relationships of Galr1

• Galanin inhibits basal and forskolin-stimulated cAMP formation in CHO cells expressing the rat GALR1 receptor via a pertussis toxin-sensitive G protein [2].
• A subset of SS neurons in the PeN appeared to express the galanin receptor mRNA, whereas few, if any, GHRH neurons appeared to do so [26].

Other interactions of Galr1

• In the present experiments, the effects of two GAL receptor antagonists, C7 and galantide, on fat consumption and central overexpression of GAL were investigated [27].
• GAL-R1 immunoreactivity was localized to cholinergic and tachykinergic neurons and to neurons immunoreactive for nitric oxide synthase or vasoactive intestinal polypeptide [28].
• Dorsal raphe glucocorticoid receptors activation by corticosterone may therefore lead to an increased signalling of 5-HT1A autoreceptors that may become counteracted by galanin receptor activation [29].
• On the same sections and only in regions of high index of galanin receptor occupancy (arcuate nucleus, median eminence, dorsomedial nucleus, paraventricular nucleus, and periventricular hypothalamic nucleus), guanyl 5'-yl imidodiphosphate paradoxically enhanced [125I]galanin binding [30].
• The rat GalR1 galanin receptor was used as a prototypic G protein-coupled receptor to test the feasibility of heterologous expression in a retrovirus-based system [31].

Analytical, diagnostic and therapeutic context of Galr1

• In situ hybridization analysis, expression of GALR1 mRNA was detected in trigeminal ganglion cells [32].
• Here we have used: 1) slice binding and quantitative autoradiography to assess the density and occupancy of GAL receptors; and 2) in situ hybridization histochemistry to assess expression of the GALR1 receptor subtype in the ventral hippocampus of 3-month-old and 21-month-old Fischer 344 male rats [16].
• Castration reduced the labeling density of galanin receptor mRNAs in POMC neurons, and testosterone prevented the effects of castration in all rostro-caudal subdivisions of the arcuate nucleus [22].
• Recent molecular cloning studies by our laboratory and others have identified the existence of a novel rat galanin receptor subtype, GALR2 [33].
• Using in situ hybridization and immunohistochemistry the expression of, respectively, prepro-galanin (pre-pro-GAL) mRNA and GAL receptor-1 mRNA, as well as GAL-like and GAL message-associated peptide-like immunoreactivities, were studied in rats from embryonic day 14 (E14) to postnatal day 1 [11].

References