Ligand- and Subtype-Selective Coupling of HumanAlpha-2 Adrenoceptors to Ca++ elevation in Chinese Hamster Ovary Cells

• Published in: The Journal of pharmacology and experimental therapeutics 1998-11, Vol.287 (2), p.667
• Main Authors: Jyrki P. Kukkonen, Annika Renvaktar, Ramin Shariatmadari, Karl E. O. Ã kerman
• Format: Article
• Language: English
• ISSN: 0022-3565; 1521-0103

The agonist profiles for Ca ++ elevations mediated by the human alpha -2 adrenoceptor subtypes alpha -2A, alpha -2B and alpha -2C were compared in the clones of Chinese hamster ovary cells expressing comparable numbers of receptors. No difference was seen between the different clones with respect to the maximum Ca ++ mobilizations or the concentrations producing half-maximal stimulation in response to noradrenaline. Ca ++ elevations were sensitive to phospholipase C inhibitor U-73122 (1-[6-([17β]-3-methoxyestra-1,3,5[10]-trien-17-yl)aminohexyl]-1H-pyrrole-2,5-dione) and pertussis toxin-pretreatment. Although noradrenaline was equally potent and active in all the clones, marked differences in the response to the other agonists were seen. UK14,304 (5-bromo-N-[4,5-dihydro-1H-imidazol-2-yl]-6-quinoxalinamine) was a full agonist (when compared to noradrenaline) for alpha -2A and alpha -2C, d -medetomidine ([+]-[S]-[4-(1-[2,3-dimethylphenyl]ethyl)-1H-imidazole]HCl) was a full agonist for alpha -2B and alpha -2C and oxymetazoline (3-[(4,5-dihydro-1H-imidazol-2-yl-)methyl]-6-[1,1-dimethylethyl]-2,4-dimethylphenol HCl) was a full agonist only for alpha -2B receptors. Clonidine (2-[2,6-dichloroaniline]-2-imidazoline HCl) was a partial agonist in all the cases; almost no response to this ligand was obtained in the alpha -2B-expressing cells. When the Ca ++ responses are compared to the previously published results on cAMP inhibition in Chinese hamster ovary cells, clonidine seems to be significantly less efficacious in elevating Ca ++ than in decreasing cAMP.