Galanin receptors and their therapeutic potential

Wang, Suke; Hwa, Joyce; Varty, Geoffrey B.

doi:10.1517/14728214.5.4.415

Cited by 6 publications

(3 citation statements)

References 146 publications

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“…Galanin mediates its effects via at least three seventransmembrane, G protein-coupled receptors (GPCRs), namely GalR1, -R2, and -R3 (14)(15)(16)(17), which have a broad distribution as revealed with RT-PCR (18) and in situ hybridization (19). GalR1 is mainly expressed in central nervous system (CNS), whereas GalR3 is restricted to a number of brain regions and some peripheral tissues and is present at low levels.…”

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confidence: 99%

“…GalR1 is mainly expressed in central nervous system (CNS), whereas GalR3 is restricted to a number of brain regions and some peripheral tissues and is present at low levels. Both GalR1 and -R3 act through G i/o receptor subtype, inhibiting adenyl cyclase, and causing hyperpolarization via opening K ϩ channels (14)(15)(16)(17). GalR2 has a broader distribution and is present in the CNS, dorsal root ganglia, and many peripheral tissues (18,19).…”

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confidence: 99%

“…Activation of GalR2 leads to accumulation of inositol phosphate, mobilization of intracellular Ca 2ϩ , and activation of a Ca 2ϩ -dependent Cl Ϫ channel via G q/11 -type G proteins. In addition, GalR2 may inhibit cAMP accumulation, through G i/o -type receptor and stimulate mitogen-activated protein kinase mediated via G o (14)(15)(16)(17).…”

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confidence: 99%

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Galanin decreases proliferation of PC12 cells and induces apoptosis via its subtype 2 receptor (GalR2)

Tofighi

Joseph

Sheng

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Galanin is a neuropeptide with a wide range of effects in the nervous and endocrine systems, mediated through three G protein-coupled receptor subtypes (GalR1-3). Interestingly, galanin and its receptors are also expressed in certain tumors. Here we studied the effects of galanin in rat pheochromocytoma (PC12) cells stably transfected with GFP-tagged GalR2. Galanin at 100 nM inhibited cell proliferation in both nontransfected and transfected cells. Conversly, both galanin and the GalR2(R3)-agonist AR-M1896 induced caspase-dependent apoptotic cell death only in GalR2-transfected cells. Western-blot analyses of downstream mediators of the G q/11-type G protein showed down-regulation of pAkt and pBad in galanin-exposed transfected cells. Also, the specific PI3 kinase inhibitor LY-294002 increased the level of pBad and decreased activation of caspases. In addition, p21 cip1 levels were up-regulated in galanin-exposed PC12 cells and down-regulated in galanin-exposed GalR2-transfected cells. In agreement, FACS analyses of galanin exposed cells showed occurrence of cell cycle arrest in PC12 cells and cell death in transfected cells. Finally, as shown with real-time PCR, galanin and its receptors were expressed at very high levels in human pheochromocytoma tissues as compared with normal adrenal medulla. These findings point to GalR2 as a possible target for therapeuthic interventions in pheochromocytoma.adrenal medulla ͉ galanin receptor ͉ neuropeptide ͉ pheochromocytoma ͉ tumor

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confidence: 99%