title: Signalling mechanism for somatostatin receptor 5-mediated suppression of AMPA responses in rat retinal ganglion cells.
abstract: Somatostatin (SRIF) is involved in a variety of physiological functions via the activation of five subtypes of specific receptors (sst1-5). Here, we investigated the effects of SRIF on AMPA receptor (AMPAR)-mediated currents (AMPA currents) in isolated rat retinal ganglion cells (GCs) using patch-clamp techniques. Immunofluorescence double labelling demonstrated the expression of sst5 in rat GCs. Consistent to this, whole cell AMPA currents of GCs were dose-dependently suppressed by SRIF, and the effect was reversed by the sst5 antagonist BIM-23056. Intracellular dialysis of GDP-β-S or pre-incubation with the Gi/o inhibitor pertussis toxin (PTX) abolished the SRIF effect. The SRIF effect was mimicked by the administration of either 8-Br-cAMP or forskolin, but was eliminated by the protein kinase A (PKA) antagonists H-89/KT5720/Rp-cAMP. Moreover, SRIF increased intracellular Ca(2+) levels and did not suppress the AMPA currents when GCs were infused with an intracellular Ca(2+)-free solution or in the presence of ryanodine receptor modulators caffeine/ryanodine. Furthermore, the SRIF effect was eliminated when the activity of calmodulin (CaM), calcineurin and protein phosphatase 1 (PP1) was blocked with W-7, FK-506 and okadaic acid, respectively. SRIF persisted to suppress the AMPA currents when cGMP-protein kinase G (PKG) and phosphatidylinositol (PI)-/phosphatidylcholine (PC)-phospholipase C (PLC) signalling pathways were blocked. In rat flat-mount retinas, SRIF suppressed AMPAR-mediated light-evoked excitatory postsynaptic currents (L-EPSCs) in GCs. We conclude that a distinct Gi/o/cAMP-PKA/ryanodine/Ca(2+)/CaM/calcineurin/PP1 signalling pathway comes into play due to the activation of sst5 to mediate the SRIF effect on GCs.
authors.affiliation: Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Deng
authors.affiliation: Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Sheng
authors.affiliation: Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: Weng
authors.affiliation: Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Xiong-Li
authors.initials: XL
authors.lastname: Yang
authors.affiliation: Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China. Electronic address: ymzhong@fudan.edu.cn.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhong
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000502:physiology*; D017481:Receptors, Somatostatin / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology
chemical_list: D018091:Receptors, AMPA; D017481:Receptors, Somatostatin; D013004:Somatostatin; C094573:somatostatin receptor 5
keywords: AMPA receptor; Neuromodulation; Retinal ganglion cells; Somatostatin; sst(5)