Vol. 287, Issue 2, 667-671, November 1998

Ligand- and Subtype-Selective Coupling of Human Alpha-2 Adrenoceptors to Ca⁺⁺ elevation in Chinese Hamster Ovary Cells¹

Jyrki P. Kukkonen , Annika Renvaktar, Ramin Shariatmadari and Karl E. O. Åkerman

Department of Physiology, Uppsala University, Uppsala, Sweden (J.P.K., R.S., K.E.O.A.) and Department of Biochemistry and Pharmacy, Åbo Akademi University, Turku, Finland (J.P.K., A.R.)

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-([17]-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.