{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T15:55:55Z","timestamp":1758815755314,"version":"3.33.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In addition to the regulation of blood pressure, \u03b1<jats:sub>2<\/jats:sub>- and \u03b2-adrenoceptor (AR) subtypes play an important role in the modulation of noradrenergic neurotransmission in the human CNS and PNS. Several studies suggest that the \u03b1<jats:sub>2<\/jats:sub>-AR responsiveness in cells and tissues after chronic epinephrine (EPI) or norepinephrine (NE) exposure may vary, depending on the \u03b2-AR activity present there. Recently, we reported that in BE(2)-C human neuroblastoma cells (endogenously expressing \u03b1<jats:sub>2A<\/jats:sub>- and \u03b2<jats:sub>2<\/jats:sub>-AR), chronic EPI treatment (300 nM) produced a dramatic \u03b2-adrenoceptor-dependent desensitization of the \u03b1<jats:sub>2A<\/jats:sub>-AR response. The aim of this study is to determine if stable addition of a \u03b2<jats:sub>2<\/jats:sub>-AR to a second neuroblastoma cell line (SH-SY5Y), that normally expresses only \u03b1<jats:sub>2A<\/jats:sub>-ARs that are not sensitive to 300 nM EPI exposure, would suddenly render \u03b1<jats:sub>2A<\/jats:sub>-ARs in that cell line sensitive to treatment with the same EPI concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>These studies employed RT-PCR, receptor binding and inhibition of cAMP accumulation to confirm \u03b1<jats:sub>2<\/jats:sub>-AR subtype expression. Stable clones of SH-SY5Y cells transfected to stably express functional \u03b2<jats:sub>2<\/jats:sub>-ARs (SH\u03b2<jats:sub>2<\/jats:sub>AR4) were selected to compare sensitivity of \u03b1<jats:sub>2<\/jats:sub>-AR to EPI in the presence or absence of \u03b2<jats:sub>2<\/jats:sub>-ARs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A series of molecular, biochemical and pharmacological studies indicated that the difference between the cell lines could not be attributed to \u03b1<jats:sub>2<\/jats:sub>-AR heterogeneity. We now report that after transfection of functional \u03b2<jats:sub>2<\/jats:sub>-AR into SH-SY5Y cells (SH\u03b2<jats:sub>2<\/jats:sub>AR4), chronic treatment with modest levels of EPI desensitizes the \u03b1<jats:sub>2A<\/jats:sub>-AR. This effect results from a \u03b2<jats:sub>2<\/jats:sub>-AR dependent down-regulation of native \u03b1<jats:sub>2A<\/jats:sub>-ARs by EPI accompanied by enhanced translocation of GRK2 and GRK3 to the membrane (required for GRK-mediated phosphorylation of agonist-occupied receptors).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study further supports the hypothesis that the presence of the \u03b2-AR renders the \u03b1<jats:sub>2A<\/jats:sub>-AR more susceptible to desensitization with physiological levels of EPI.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2210-7-16","type":"journal-article","created":{"date-parts":[[2007,12,20]],"date-time":"2007-12-20T19:37:04Z","timestamp":1198179424000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The presence of \u03b22-adrenoceptors sensitizes \u03b12A-adrenoceptors to desensitization after chronic epinephrine treatment"],"prefix":"10.1186","volume":"7","author":[{"given":"Tasneem","family":"Bawa-Khalfe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghazi F","family":"Altememi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chitra D","family":"Mandyam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay A","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas C","family":"Eikenburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly M","family":"Standifer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,12,20]]},"reference":[{"issue":"4","key":"232_CR1","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1111\/j.1476-5381.1990.tb14078.x","volume":"100","author":"GW John","year":"1990","unstructured":"John GW, Doxey JC, Walter DS, Reid JL: The role of alpha- and beta-adrenoceptor subtypes in mediating the effects of catecholamines on fasting glucose and insulin concentrations in the rat. 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