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Galanin-like Peptide-A New Obesity Related Peptide

Effects of galanin-like Peptide on food intake and the hypothalamo-pituitary-thyroid axis
Galanin-like peptide (GALP) is a novel hypothalamic peptide synthesised in neurons in the arcuate nucleus which project to the paraventricular nucleus (PVN). GALP has recently been identified as an orexigenic peptide. In this study we aimed to further characterise the hypothalamic action of this peptide in energy homeostasis. Firstly, we investigated the orexigenic effect of GALP in the PVN and compared its effects with galanin and galanin 2-29. Secondly, we examined the effect of PVN administration of GALP and galanin on circulating thyroid-stimulating hormone (TSH). PVN administration of GALP significantly increased the food intake of satiated rats 1 h after administration at doses of 0.3, 1 and 3 nmol. In comparison with paraventricular administration of galanin, GALP was a more potent orexigen, whereas galanin 2-29, the relatively selective GAL R2 agonist, had no effect on food intake. Both GALP and galanin administration (1 nmol) into the PVN significantly decreased the level of circulating TSH. To investigate the mechanism of these effects, we examined the effect of GALP and galanin application on neuropeptide release from hypothalamic explants in vitro. GALP peptide (100 nM) stimulated the release of the orexigenic peptide neuropeptide Y from hypothalamic explants and decreased the release of the anorectic peptide cocaine-and-amphetamine-regulated transcript, whereas galanin (100 nM) peptide had no significant effect on the release of either peptide. Both GALP (100 nM) and galanin (100 nM) inhibited the release thyrotrophin-releasing hormone. These data suggest that in the PVN, GALP may play a role in energy homeostasis by stimulating food intake and suppressing TSH release.

Seth A, Stanley S, Dhillo W, Murphy K, Ghatei M, Bloom S. Neuroendocrinology 2003 Feb;77(2):125-31

A role for galanin-like Peptide in the integration of feeding, body weight regulation, and reproduction in the mouse
Galanin-like peptide (GALP) shares sequence homology with galanin and binds to galanin receptors in vitro. GALP neurons in the arcuate nucleus coexpress leptin receptors, and GALP mRNA expression is up-regulated by leptin. Based on these observations, we postulated that GALP plays a role in mediating leptin's inhibitory effects on food intake (FI) and body weight (BW), as well as its stimulatory effect on the reproductive axis. To test these hypotheses, we performed several studies in which mice received intracerebroventricular injections of either GALP or vehicle. Acute GALP treatment elicited a dose-dependent suppression of FI and BW. Long-term treatment with GALP caused only transient reductions in FI and BW, demonstrating that the mice became refractory to continued exposure to GALP. GALP inhibited FI as early as 1 h post injection. Central injection of GALP suppressed locomotor activity and elicited the formation of a conditioned taste aversion. In male mice, serum levels of LH and testosterone were increased by GALP administration. Although we cannot rule out possible nonspecific effects of GALP on FI, the present observations are consistent with the argument that GALP is a downstream effector of leptin's actions within the central nervous system.

Krasnow SM, Fraley GS, Schuh SM, Baumgartner JW, Clifton DK, Steiner RA. Endocrinology 2003 Mar;144(3):813-22

Galanin-like peptide stimulates food intake in the rat
We have isolated a novel hypothalamic peptide, Galanin-like peptide (GALP), as a ligand for galanin receptor subtype GalR2. To investigate the physiological role of GALP, we examined the effect of the intracerebroventricular administration of GALP and found that GALP induced food intakes. GALP had ten-fold the orexigenic activity of galanin. We also observed the anxiogenic-like behavior after the administration of 1 nmol GALP. These results suggest that GALP is a novel orexigenic and anxiogenic peptide. 

Matsumoto Y, et. al., Neurosci Lett 2002 Mar 29;322(1):67-9

Centrally administered galanin-like peptide modifies food intake in the rat: a comparison with galanin
Galanin-like peptide (GALP) is a recently identified neuropeptide that shares sequence homology with the orexigenic neuropeptide, galanin. In contrast to galanin, GALP is reported to bind preferentially to the galanin receptor 2 subtype (GalR2) compared to GalR1. The aim of this study was to determine the effect of GALP on feeding, body weight and core body temperature after central administration in rats compared to the effects of galanin. Intracerebroventricular (i.c.v.) injection of GALP (1 micro g-10 micro g) significantly stimulated feeding at 1 h in both satiated and fasted Sprague-Dawley rats. However, 24 h after GALP injection, body weight gain was significantly reduced and food intake was also usually decreased. In addition, i.c.v. GALP caused a dose-related increase in core body temperature, which lasted until 6-8 h after injection, and was reduced by peripheral administration of the cyclooxygenase inhibitor, flurbiprofen (1 mg/kg). Similar to GALP, i.c.v. injection of galanin (5 micro g) significantly increased feeding at 1 h in satiated rats. However, there was no difference in food intake and body weight at 24 h, and galanin only caused a transient rise in body temperature. Thus, similar to galanin, GALP has an acute orexigenic effect on feeding. However, GALP also has an anorectic action, which is apparent at a later time. Therefore, GALP has complex opposing actions on energy homeostasis.

Lawrence CB, Baudoin FM, Luckman SM. J Neuroendocrinol 2002 Nov;14(11):853-60

1. Jureus A, Cunningham MJ, McClain ME, Clifton DK, Steiner RA. Galanin-like peptide (GALP) is a target for regulation by leptin in the hypothalamus of the rat. Endocrinology 2000 Jul;141(7):2703-6

Galanin-like peptide (GALP), which was recently isolated from the porcine hypothalamus, shares sequence homology with galanin and binds with high affinity to galanin receptors. To study the distribution and regulation of GALP-expressing cells in the brain, we cloned a 120 base-pair cDNA fragment of rat GALP and produced an antisense riboprobe. In situ hybridization for GALP mRNA was then performed on tissue sections throughout the forebrain of adult ovariectomized female rats. We found GALP mRNA-containing cells in the arcuate nucleus (Arc), caudal dorsomedial nucleus, median eminence and the pituitary. Because GALP mRNA in the Arc appeared to overlap with the known distribution of leptin receptor mRNA, we tested the hypothesis that GALP expression is regulated by leptin. Using in situ hybridization, we compared the number of GALP mRNA-containing cells among groups of rats that were fed ad lib or fasted for 48 h and treated with either leptin or vehicle. Fasting reduced the number of identifiable cells containing GALP mRNA in the Arc, whereas the treatment of fasted animals with leptin produced a 4-fold increase in the number of cells expressing GALP message. The presence of GALP mRNA in the hypothalamus and pituitary and its regulation by leptin suggests that GALP may have important neuroendocrine functions, including the physiological regulation of feeding, metabolism, and reproduction

2. Ohtaki T, Kumano S, Ishibashi Y, Ogi K, Matsui H, Harada M, Kitada C, Kurokawa T, Onda H, Fujino M. Isolation and cDNA cloning of a novel galanin-like peptide (GALP) from porcine hypothalamus. J Biol Chem 1999 Dec 24;274(52):37041-5

3. Wang ZL, Kulkarni RN, Wang RM, Smith DM, Ghatei MA, Byfield PG, Bennet WM, Bloom SR. Possible evidence for endogenous production of a novel galanin-like peptide.
J Clin Invest 1997 Jul 1;100(1):189-96

5~ 10 ng of GALP (H) and GALP (Rat) can be detected on dot blot system!!!

Supersensitive Assay for GALP-ir

 

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