title: Functional alpha2C-adrenoceptors in human neuroblastoma SH-SY5Y cells.
abstract: The alpha2-adrenoceptor mediating inhibition of forskolin-stimulated cyclic AMP accumulation in human neuroblastoma SH-SY5Y cells was further characterized. The alpha2-adrenoceptor agonists, UK 14,304 (5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline), oxymetazoline, guanfacine, (-)-noradrenaline and clonidine concentration-dependently decreased cyclic AMP accumulation in this cell line (Emax ca. 50% inhibition). Agonist pEC50 values ranged between 6.7 and 7.8. Clonidine was a partial agonist. The effects of UK 14,304 were blocked after a pertussis toxin treatment. The concentration-response curves of UK 14,304 were shifted to the right in a parallel manner by the following antagonists (mean pK(B) values): yohimbine (8.17), idazoxan (7.63), prazosin (6.66), 2-[2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2 H,4H) isoquinolindione (ARC 239; 7.12) and 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB-4101; 8.12). The relatively high pKB values of prazosin and ARC 239 point to a non-alpha2A-adrenoceptor-mediated effect. The relatively high pK(B) value of WB-4101 further characterizes the alpha2-adrenoceptor in SH-SY5Y cells as being of the alpha2C subtype. The analysis of the expression of alpha2-adrenoceptor subtypes by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the exclusive presence of alpha2C-adrenoceptor mRNA in SH-SY5Y cells. We propose that inhibition of forskolin-stimulated cAMP accumulation in SH-SY5Y cells be used as a functional model of human, native alpha2C-adrenoceptors.
authors.affiliation: Nervous System Therapeutic Area, Novartis Pharma Research, Novartis Pharma, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Parsley
authors.forename: L
authors.initials: L
authors.lastname: Gazi
authors.forename: I
authors.initials: I
authors.lastname: Bobirnac
authors.forename: E
authors.initials: E
authors.lastname: Loetscher
authors.forename: P
authors.initials: P
authors.lastname: Schoeffter
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016316:Guanfacine / Q000494:pharmacology; D006801:Humans; D019329:Idazoxan / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009447:Neuroblastoma; D010109:Oxymetazoline / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: C547771:ADRA2B protein, human; C547774:ADRA2C protein, human; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007546:Isoquinolines; D010879:Piperazines; D011810:Quinoxalines; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2; D005576:Colforsin; D015016:Yohimbine; D016316:Guanfacine; D000068438:Brimonidine Tartrate; D010109:Oxymetazoline; D000242:Cyclic AMP; C032994:AR-C239; D003000:Clonidine; D011224:Prazosin; D019329:Idazoxan