Alpha-2A and alpha-2B adrenergic receptor subtypes: attenuation of cyclic AMP production in cell lines containing only one receptor subtype.
At least two subtypes of alpha-2 adrenergic receptors have been identified on the basis of antagonist affinities as determined mainly by radioligand binding assays. The human platelet and the HT29 human colonic adenocarcinoma cell contain alpha-2A adrenergic receptors, whereas the neonatal rat lung and the NG108 neuroblastoma X glioma hybrid cell contain the alpha-2B adrenergic receptor. Using the attenuation of the cyclic AMP accumulation as a functional assay, the affinities of various antagonists for the alpha-2 adrenergic receptor were determined in HT29 and NG108 cell lines. Dose-response curves to 5-bromo-6-(2-imidazoline-2-yl-amino)quinoxaline (UK 14,304) an alpha-2 adrenergic agonist, were generated in the absence and presence of three concentrations of various antagonists. Schild regressions were used to determine pA2 values and then dissociation constants (KB value) were calculated. Whereas phentolamine and yohimbine were equipotent at the receptor in the two cell lines, 2-(2,4-(O-methoxyphenyl)-piper-azin-1-yl)ethyl-4,4-dimethyl-1,3-(2 H,4H)- isoquinolindione (ARC-239) and prazosin were 100- and 30-fold more potent in the NG108 cell line than in the HT29 cell. These potency ratios determined from functional experiments are the same as those obtained from radioligand binding experiments. These functional data are consistent with the previous and more extensive binding data, and thus support the existence and definition of alpha-2A and alpha-2B adrenergic receptor subtypes.
Bylund
D B
DB
Department of Pharmacology, School of Medicine, University of Missouri-Columbia.
Ray-Prenger
C
C
D000818:Animals; D000068438:Brimonidine Tartrate; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000502:physiology*; D014407:Tumor Cells, Cultured; D015016:Yohimbine / Q000494:pharmacology
D007546:Isoquinolines; D010879:Piperazines; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D000242:Cyclic AMP; C032994:AR-C239; D011224:Prazosin