Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 1034
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Although up-regulation of β-adrenergic receptors (β-ARs) occurs after long-term use of their antagonists in various tissues, the available data are little on mechanisms of β-AR up-regulation induced by their continuous blockade. The present study attempted to clarify mechanisms of β-AR up-regulation using mouse cerebral cortical neurons continuously exposed to nadolol (10 nM), a non-selective β-AR antagonist, for 24 h. Nadolol dose-dependently induced both subtypes of β-ARs, β₁- and β₂-ARs, which were not suppressed by protein A kinase inhibition with KT5720. On the other hand, blockade of α₁-ARs, which are immunohistochemically confirmed to be co-localized with β-ARs in the same neurons, significantly inhibited only β₁-AR up-regulation and the expression of β₂-ARs did not alter. In addition, phenylephrine, an agonist specific to α₁-ARs up-regulated β₁-ARs, but not β₂-ARs. Under the conditions with β-AR up-regulation, the level of phosphorylated protein kinase Cα (pPKCα) increased, which is significantly suppressed by prazosin, an α1-AR antagonist. Furthermore, nadolol decreased the degradation of mRNA of β₁-ARs, but not β₂-ARs. These results indicate that the nadolol-induced β₁-AR up-regulation is mediated via PKC-relating pathway via α₁-AR activation with stabilizing β₁-AR mRNA and that the increased expression of β₂-ARs is regulated by pathways different from those for β₁-AR expression.
Download full-text PDF |
Source |
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http://dx.doi.org/10.1016/j.brainres.2011.07.057 | DOI Listing |
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