title: Angiotensin II AT2 receptors regulate NGF-mediated neurite outgrowth via the NO-cGMP pathway.
abstract: We investigated whether Angiotensin II type 2 (AT2) receptor activation was involved in NGF-induced nerve regeneration. NGF-mediated neurite outgrowth in cultured dorsal root ganglia (DRG) cells was significantly inhibited by AT2 receptor antagonist (PD123,319) treatment. AT2 receptor knockdown also inhibited NGF-mediated neurite outgrowth. To determine the mechanisms, we analyzed the NO-cGMP pathway. The cGMP analog increased NGF-mediated nerve elongation, which inhibited by PD123,319. Furthermore, soluble guanylate cyclase expression was significantly less in NGF and PD123,319 treatment DRG than in NGF treatment alone. These results suggest that NGF-mediated neurite outgrowth is suppressed by AT2 receptor signaling via the NO-cGMP-PKG pathway.
authors.affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama, 700-0005, Japan. Electronic address: hobara@dls.ous.ac.jp.
authors.forename: Narumi
authors.initials: N
authors.lastname: Hashikawa-Hobara
authors.affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama, 700-0005, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hashikawa
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility
chemical_list: D007093:Imidazoles; D020030:Nitric Oxide Donors; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; C073402:PD 123319; D009569:Nitric Oxide; D020932:Nerve Growth Factor; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D015740:Calcitonin Gene-Related Peptide
keywords: Angiotensin II; Angiotensin II type 2 receptor; NO-cGMP; Nerve growth factor