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10.1371/journal.pone.0179345 http://scihub22266oqcxt.onion/10.1371/journal.pone.0179345 C5464668!5464668 !28594895     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28594895 &cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28594895 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       PLoS+One 2017 ; 12 (6 ): e0179345 Nephropedia Template TP {{tp|p=28594895 |t=2017. ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandil lower intraocular pressure by activating the Erk1/2 signaling pathway |pdf=|usr=}}{{28594895 }} gab.com Text ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandil lower intraocular pressure by activating the Erk1/2 signaling pathway JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28594895 #FOAvip Elevated intraocular pressure is the most prevalent and only treatable risk factor for glaucoma, a degenerative disease of the optic nerve. While treatment options to slow disease progression are available, all current therapeutic and surgical treatments have unwanted side effects or limited efficacy, resulting in the need to identify new options. Previous reports from our laboratory have established a novel ocular hypotensive effect of ATP-sensitive potassium channel (KATP) openers including diazoxide (DZ) and nicorandil (NCD). In the current study, we evaluated the role of Erk1/2 signaling pathway in KATP channel opener mediated reduction of intraocular pressure (IOP). Western blot analysis of DZ and NCD treated primary normal trabecular meshwork (NTM) cells, human TM (isolated from perfusion cultures of human anterior segments) and mouse eyes showed increased phosphorylation of Erk1/2 when compared to vehicle treated controls. DZ and NCD mediated pressure reduction (p<0.02) in human anterior segments (n = 7 for DZ, n = 4 for NCD) was abrogated by U0126 (DZ + U0126: -9.7 ± 11.5%, p = 0.11; NCD + U0126: -0.1 ± 11.5%, p = 1.0). In contrast, U0126 had no effect on latanoprostfree acid-induced pressure reduction (-52.5 ± 6.8%, n = 4, p = 0.001). In mice, DZ and NCD reduced IOP (DZ, 14.9 ± 3.8%, NCD, 16.9 ± 2.5%, n = 10, p<0.001), but the pressure reduction was inhibited by U0126 (DZ + U0126, 0.7 ± 3.0%; NCD + U0126, 0.9 ± 2.2%, n = 10, p>0.1). Histologic evaluation of transmission electron micrographs from DZ + U0126 and NCD + U0126 treated eyes revealed no observable morphological changes in the ultrastructure of the conventional outflow pathway. Taken together, the results indicate that the Erk1/2 pathway is necessary for IOP reduction by KATP channel openers DZ and NCD. Twit Text FOAVip ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandil lower intraocular pressure by activating the Erk1/2 signaling pathway ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=28594895 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28594895 #FOAvip English Wikipedia <ref>{{Cite pmid|28594895 }}</ref> ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandil lower intraocular pressure by activating the Erk1/2 signaling pathway #MMPMID28594895 Roy Chowdhury U ; Bahler CK ; Holman BH ; Fautsch MP PLoS One 2017[]; 12 (6 ): e0179345 PMID28594895 show ga Elevated intraocular pressure is the most prevalent and only treatable risk factor for glaucoma, a degenerative disease of the optic nerve. While treatment options to slow disease progression are available, all current therapeutic and surgical treatments have unwanted side effects or limited efficacy, resulting in the need to identify new options. Previous reports from our laboratory have established a novel ocular hypotensive effect of ATP-sensitive potassium channel (KATP) openers including diazoxide (DZ) and nicorandil (NCD). In the current study, we evaluated the role of Erk1/2 signaling pathway in KATP channel opener mediated reduction of intraocular pressure (IOP). Western blot analysis of DZ and NCD treated primary normal trabecular meshwork (NTM) cells, human TM (isolated from perfusion cultures of human anterior segments) and mouse eyes showed increased phosphorylation of Erk1/2 when compared to vehicle treated controls. DZ and NCD mediated pressure reduction (p<0.02) in human anterior segments (n = 7 for DZ, n = 4 for NCD) was abrogated by U0126 (DZ + U0126: -9.7 ± 11.5%, p = 0.11; NCD + U0126: -0.1 ± 11.5%, p = 1.0). In contrast, U0126 had no effect on latanoprostfree acid-induced pressure reduction (-52.5 ± 6.8%, n = 4, p = 0.001). In mice, DZ and NCD reduced IOP (DZ, 14.9 ± 3.8%, NCD, 16.9 ± 2.5%, n = 10, p<0.001), but the pressure reduction was inhibited by U0126 (DZ + U0126, 0.7 ± 3.0%; NCD + U0126, 0.9 ± 2.2%, n = 10, p>0.1). Histologic evaluation of transmission electron micrographs from DZ + U0126 and NCD + U0126 treated eyes revealed no observable morphological changes in the ultrastructure of the conventional outflow pathway. Taken together, the results indicate that the Erk1/2 pathway is necessary for IOP reduction by KATP channel openers DZ and NCD. |Adult [MESH] |Aged [MESH] |Aged, 80 and over [MESH] |Animals [MESH] |Butadienes/pharmacology [MESH] |Cells, Cultured [MESH] |Diazoxide/*pharmacology [MESH] |Enzyme Activation/drug effects [MESH] |Humans [MESH] |Infant [MESH] |Intraocular Pressure/*drug effects [MESH] |Ion Channel Gating/*drug effects [MESH] |KATP Channels/*metabolism [MESH] |MAP Kinase Signaling System/*drug effects [MESH] |Mice, Inbred C57BL [MESH] |Middle Aged [MESH] |Nicorandil/*pharmacology [MESH] |Nitriles/pharmacology [MESH] |Ocular Hypotension/physiopathology [MESH] |Perfusion [MESH]ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandi(epmc).pdf DeepDyve Pubget Overpricing