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Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission.
Zhao Z, Wan L, Liu X, Huo F, Li H, Barry D, Krieger S, Kim S, Liu Z, Xu J, Rogers B, Li Y, Chen Z (2014) Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission. J Neurosci 34:12402-12414. doi: 10.1523/JNEUROSCI.1709-14.2014
Summary: After itch detection, the itch pathway moves through an array of G-protein coupled receptors and transient receptor potential channels in dorsal root ganglion neurons into dorsal horn neurons which integrate and transduce these signals, sending them to the somatosensory cortex. The purpose of this work is to clarify whether gastrin-releasing peptide (GRP) or B-type natriuretic peptide regulates histaminergic itch. Several strains of knockout mice received 200, 300, or 400 ng intrathecal injections of bombesin-SAP (Cat. #IT-40). Blank-SAP (Cat. #IT-21) was used as a control. The data further define the respective functions of the neuromedin B receptor and GRP receptor in itch, and reveals a working relationship between the different interneuron populations.
Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)
Orexin A activates hypoglossal motoneurons and enhances genioglossus muscle activity in rats.
Zhang G, Liu Z, Zhang B, Geng W, Song N, Zhou W, Cao Y, Li S, Huang Z, Shen L (2014) Orexin A activates hypoglossal motoneurons and enhances genioglossus muscle activity in rats. Br J Pharmacol 171:4233-4246. doi: 10.1111/bph.12784
Summary: Orexin neurons are restricted to the lateral hypothalamus (LH) and are involved in functions such as feeding behavior, energy homeostasis, sleep/wake cycles, and many others. Here the authors investigate orexin control of the genioglossus – the largest upper airway dilator muscle. Rats received bilateral 172 ng injections of orexin-SAP into the LH. Lesioned animals displayed a significant decrease in genioglossus muscle electromyograms, indicating that orexin neurons are vital to the control of this muscle.
Related Products: Orexin-B-SAP (Cat. #IT-20)
Effects of GLP-1 on appetite and weight
Shah M, Vella A (2014) Effects of GLP-1 on appetite and weight. Rev Endocr Metab Disord 15(3):181-187. doi: 10.1007/s11154-014-9289-5 PMID: 24811133
Objective: To determine if the synergistic actions of GLP-1 in the gut and brain, acting on both central and peripheral receptors are responsible for the effects of the hormone on satiety.
Summary: The effect of GLP-1 on satiety is primarily derived from its action on anorexigenic hormones so that when NPY/ AgRP neurons are specifically eliminated by NPY-SAP, the effect of GLP-1 on decreasing satiation persists.
Related Products: NPY-SAP (Cat. #IT-28)
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High-content analysis of antibody phage-display library selection outputs identifies tumor selective macropinocytosis-dependent rapidly internalizing antibodies.
Ha K, Bidlingmaier S, Zhang Y, Su Y, Liu B (2014) High-content analysis of antibody phage-display library selection outputs identifies tumor selective macropinocytosis-dependent rapidly internalizing antibodies. Mol Cell Proteomics 13:3320-3331. doi: 10.1074/mcp.M114.039768
Summary: Macropinocytosis, the internalization of large endocytic vesicles called macropinosomes, is upregulated in Ras-transformed cancers. To date, large-scale antibody generation strategies have not incorporated a selection method for antibodies. In this work the authors demonstrate screening and validation of the antibodies that utilize the macropinosome pathway. One method used was to biotinylate the antibodies and combine them with Streptavidin-ZAP (Cat. #IT-27) at a 1:1 ratio. The conjugate was applied to cells in a concentration curve starting at 200 nM in order to demonstrate internalization and cell killing.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Effects of noradrenergic denervation by anti-DBH-saporin on behavioral responsivity to L-DOPA in the hemi-parkinsonian rat.
Ostock C, Lindenbach D, Goldenberg A, Kampton E, Bishop C (2014) Effects of noradrenergic denervation by anti-DBH-saporin on behavioral responsivity to L-DOPA in the hemi-parkinsonian rat. Behav Brain Res 270:75-85. doi: 10.1016/j.bbr.2014.05.009
Summary: Dopamine loss is central to Parkinson’s disease and is often accompanied by noradrenergic denervation of the locus coeruleus. In this work the authors examined the role this loss plays in L-DOPA therapy using a rat Parkinson’s disease model. The rats received 10 μg of anti-DBH-SAP (Cat. #IT-03) into the left lateral ventricle. Loss of norepinephrine (NE) neurons did not affect behavior, but lesioned animals were less responsive to the pro-motor therapeutic effects of L-DOPA.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and β-cell regeneration in mice.
Criscimanna A, Coudriet G, Gittes G, Piganelli J, Esni F (2014) Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and β-cell regeneration in mice. Gastroenterology 147:1106-1118.e1111. doi: 10.1053/j.gastro.2014.08.008
Summary: In response to tissue damage or infection, monocytes are recruited to the injured area and differentiate into macrophages. These macrophages can perform different functions depending on the tissue type. The specific differentiation macrophages undergo in response to their environment is called polarization. The authors used a mouse pancreatic lesion model to examine the polarization of macrophages into the two distinct states known, M1 and M2. Mice received 20 μg of Mac-1-SAP mouse (Cat. #IT-06) in a tail vein injection following a pancreatic lesion, and were sacrificed on various days post-injection in order to evaluate macrophage presence at different response stages. The results demonstrate that various aspects of macrophage polarization are required for pancreatic regeneration.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission.
Liu H, Yan W, Lu X, Zhang X, Wei J, Wang X, Wang T, Wu T, Cao J, Shao C, Zhou F, Zhang H, Zhang P, Zang T, Lu X, Cao J, Ding H, Zhang L (2014) Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission. Exp Neurol 261:475-485. doi: 10.1016/j.expneurol.2014.07.018
Summary: The first synapse in the pain pathway is in the spinal dorsal horn, and several sites are involved in the descending control of pain. Previous studies have suggested that cerebrospinal fluid-contacting neurons may facilitate signal transmission and substance transport between the brain parenchyma and the CSF, including processes that modulate pain transmission. The authors administered CTB-SAP (Cat. #IT-14) into the right lateral ventricle of rats. Saporin (Cat. #PR-01) was used as a control. The results indicate that the 5-HT pathway contacting the CSF is an important piece in the descending inhibitory system controlling spinal transmission of pain.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Light-triggered, efficient cytosolic release of IM7-saporin targeting the putative cancer stem cell marker CD44 by photochemical internalization.
Bostad M, Kausberg M, Weyergang A, Olsen C, Berg K, Høgset A, Selbo P (2014) Light-triggered, efficient cytosolic release of IM7-saporin targeting the putative cancer stem cell marker CD44 by photochemical internalization. Mol Pharm 11:2764-2776. doi: 10.1021/mp500129t
Summary: CD44 is known as a common cancer stem cell (CSC) marker. Given that CSC’s seem to have the ability to resist many therapeutic agents, the authors investigated the use of photochemical internalization (PCI) while targeting CD44-expressing CSC’s. An immunotoxin was constructed by biotinylating a pan CD44 antibody and combining it with Streptavidin-ZAP (Cat. #IT-27) at a 4:1 biotinylated antibody to Streptavidin-ZAP molar ratio. Various cancer cell lines were incubated with the toxin at a concentration of 0.825 nM. The toxin showed specific cytotoxicity to CD44-expressing cell lines, demonstrating the efficacy of PCI in conjunction with targeted toxins to treat some cancers
Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD44-SAP (Cat. #IT-72)
P2Y1 receptor-mediated potentiation of inspiratory motor output in neonatal rat in vitro.
Alvares T, Revill A, Huxtable A, Lorenz C, Funk G (2014) P2Y1 receptor-mediated potentiation of inspiratory motor output in neonatal rat in vitro. J Physiol 592:3089-3111. doi: 10.1113/jphysiol.2013.268136 PMID: 24879869
Summary: P2YR’s are metabotropic purinergic receptors found in some parts of the CNS. A subtype of this receptor excites rhythm generating networks in the preBötzinger complex. In order to better understand the role of these receptors in modulation of motor output the authors used brainstem-spinal cord and medullary slice preparations from neonatal rats to investigate P2Y1R signaling on specific neurons that innervate diaphragm and airway muscles. Anti-NK1r (Cat. #AB-N33AP) at a 1:1000 dilution was used during the immunohistochemistry. The data suggest that loss of purinergic modulation contributes to motoneuron excitability.
Related Products: NK-1 Receptor Rabbit Polyclonal, affinity-purified (Cat. #AB-N33AP)
Featured Article: Corticotropin releasing factor-saporin conjugate selectively lesions nucleus incertus
Lee CL, Rajkumar R, Dawe GS (2014) Featured Article: Corticotropin releasing factor-saporin conjugate selectively lesions nucleus incertus. Targeting Trends 15(2)
Related Products: CRF-SAP (Cat. #IT-13), Blank-SAP (Cat. #IT-21)
Read the featured article in Targeting Trends.
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