A comparative analysis of human and mouse islet G-protein coupled receptor expression.

G-protein coupled receptors (GPCRs) are essential for islet function, but most studies use rodent islets due to limited human islet availability. We have systematically compared the GPCR mRNA expression in human and mouse islets to determine to what extent mouse islets can be used as surrogates for human islets to study islet GPCR function, and we have identified species-specific expression of several GPCRs. The A3 receptor (ADORA3) was expressed only in mouse islets and the A3 agonist MRS 5698 inhibited glucose-induced insulin secretion from mouse islets, with no effect on human islets. Similarly, mRNAs encoding the galanin receptors GAL1 (GALR1), GAL2 (GALR2) and GAL3 GALR3) were abundantly expressed in mouse islets but present only at low levels in human islets, so that it reads (GALR3) and galanin inhibited insulin secretion only from mouse islets. Conversely, the sst1 receptor (SSTR1) was abundant only in human islets and its selective activation by CH 275 inhibited insulin secretion from human islets, with no effect on mouse islets. Our comprehensive human and mouse islet GPCR atlas has demonstrated that species differences do exist in islet GPCR expression and function, which are likely to impact on the translatability of mouse studies to the human context.

Expression of galanin and its receptors are perturbed in a rodent model of mild, blast-induced traumatic brain injury.

The symptomatology, mood and cognitive disturbances seen in post-traumatic stress disorder (PTSD) and mild blast-induced traumatic brain injury (mbTBI) overlap considerably. However the pathological mechanisms underlying the two conditions are currently unknown. The neuropeptide galanin has been suggested to play a role in the development of stress and mood disorders. Here we applied bio- and histochemical methods with the aim to elucidate the nature of any changes in the expression of galanin and its receptors in a rodent model of mbTBI. In situ hybridization and quantitative polymerase chain reaction studies revealed significant, injury-induced changes, in some cases lasting at least for one week, in the mRNA levels of galanin and/or its three receptors, galanin receptor 1-3 (GalR1-3). Such changes were seen in several forebrain regions, and the locus coeruleus. In the ventral periaqueductal gray GalR1 mRNA levels were increased, while GalR2 were decreased. Analysis of galanin peptide levels using radioimmunoassay demonstrated an increase in several brain regions including the locus coeruleus, dorsal hippocampal formation and amygdala. These findings suggest a role for the galanin system in the endogenous response to mbTBI, and that pharmacological studies of the effects of activation or inhibition of different galanin receptors in combination with functional assays of behavioral recovery may reveal promising targets for new therapeutic strategies in mbTBI.

Expression of galanin and the galanin receptor in rat taste buds.

Galanin, a 29-amino-acid neuropeptide, was initially isolated from porcine intestine. It has a wide spread distribution in the central nervous system and is also present in the primary sensory neuron. Galanin has been suggested to be involved in numerous neuronal and endocrine functions as a neurotransmitter and neuromodulator. We examined the expression of galanin and galanin receptors by using a reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridization. RT-PCR analysis showed that mRNA of galanin and GalR2 were detected in the taste bud-containing epithelium of the circumvallate papilla of rats. Immunohistochemical analyses detected galanin was detected in a subset of taste bud cells of the circumvallate papillae. Double-label studies showed that galanin colocalized with alpha-gustducin, NCAM, and PLCbeta2. Our results of double staining with galanin and taste cell markers indicate that galanin-expressing taste cells are type II and type III cells. Taken together with previous studies, these findings show that galanin may function as a taste bud neurotransmitter. Furthermore, GalR2 mRNA was expressed in some taste bud cells. This suggests that, galanin release may not only excite the peripheral afferent nerve fiber but also may act on neighboring taste receptor cells via the activation of GalR2.

Cloning and characterization of a novel G-protein-coupled receptor with homology to galanin receptors.

We report the identification, cloning, and localization of human and mouse orthologues of a new G-protein-coupled receptor with homology to galanin receptors, which we termed galanin-receptor like (GalRL). The genes of GalRL were localized to chromosome 5q32 in human and to 18B3 in mouse. Northern blot analysis revealed expression of GalRL in the central nervous system of human and mouse and in 7- and 15-day-old mouse embryos. Minor levels were found in some peripheral organs and tissues, such as testis, liver, kidney and stomach. In situ hybridization experiments demonstrated predominant expression of GalRL in the central nervous system, with a distinct localization in the habenular complex. In the peripheral nervous system single neurons of sensory ganglia were labeled. During embryonal development the expression was more widespread in the nervous system, where in addition to the dorsal thalamus, hybridization signals were detected in other areas of the brain including the striatum, the locus coeruleus, and several hindbrain nuclei. A weak activation of GalRL by galanin suggests that the endogenous ligand shares structural features with galanin.