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Activation of somatostatin receptor 5 suppresses T-type Ca 2+ channels through NO/cGMP/PKG signaling pathway in rat retinal ganglion cells

Activation of somatostatin receptor 5 suppresses T-type Ca 2+ channels through NO/cGMP/PKG signaling pathway in rat retinal ganglion cells

Qian Li, Yi Zhang, Na Wu, Ning Yin, Xing-Huai Sun, Zhongfeng Wang

Neurosci Lett. 2019 Aug 24;708:134337.

PMID: 31220522

Abstract:

Somatostatin has been shown to modulate a variety of neuronal functions by activating the five specific G-protein coupled receptors (sst1-sst5). Here, effects of sst5 receptor activation on T-type Ca2+ channels in acutely isolated retinal ganglion cells (RGCs) of rats were investigated using whole-cell patch-clamp techniques. The sst5 receptor specific agonist L-817,818 significantly and reversibly suppressed T-type Ca2+ currents, and shifted inactivation curve of the channels toward hyperpolarization direction. The effect of L-817,818 was in a dose-dependent manner, with an IC50 being 8.8 μM. Pertussis toxin-sensitive Gi/o protein mediated intracellular nitric oxide (NO)/cGMP/protein kinase G (PKG) signaling cascade was involved in the L-817,818 effect on Ca2+ currents because pharmacological interference of each of these signaling molecules abolished the L-817,818 effect. In contrast, neither phospholipase C/protein kinase C nor cAMP/protein kinase A signal pathways seemed likely to be involved because the L-817,818 effect persisted when these signaling pathways were blocked by U73122, bisindolylmaleimide IV, chelerythrine chloride, and Rp-cAMP, respectively. These results suggest that activation of sst5 receptors suppresses T-type Ca2+ currents in rat RGCs through intracellular NO/cGMP/PKG signaling pathway, which may provide a potential mechanism for protecting RGCs against injury.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP119139230-A	Bisindolylmaleimide IV		119139-23-0	Price

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