LIGAND-SELECTIVE AND SUBTYPE-SELECTIVE COUPLING OF HUMAN ALPHA-2-ADRENOCEPTORS TO CA-HAMSTER OVARY CELLS(+ ELEVATION IN CHINESE)

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 numbe rs of receptors. No difference was seen between the different clones w ith respect to the maximum Ca++ mobilizations or the concentrations pr oducing half-maximal stimulation in response to noradrenaline. Ca++ el evations were sensitive to phospholipase C inhibitor U-73122 (1-[6-([1 7 [10]-trien-17-yl)aminohexyl]-1H-pyrrole-2,5-dione) and pertussis tox in-pretreatment. Although noradrenaline was equally potent and active in all the clones, marked differences in the response to the other ago nists were seen. UK14,304 -[4,5-dihydro-1H-imidazol-2-yl]-6-quinoxalin amine) was a full agonist (when compared to noradrenaline) for alpha-2 A and alpha-2C, D-medetomidine [4-(1-[2,3-dimethylphenyl]ethyl)-1H-imi dazole]HCl) was a full agonist for alpha-2B and alpha-2C and oxymetazo line -)methyl]-6-[1,1-dimethylethyl]-2,4-dimethylphenol HCl) was a ful l agonist only for alpha-2B receptors. Clonidine (2-[2,6-dichloroanili ne]-2-imidazoline HCl) was a partial agonist in all the cases; almost no response to this ligand was obtained in the alpha-2B-expressing cel ls. When the Ca++ responses are compared to the previously published r esults on cAMP inhibition in Chinese hamster ovary cells, clonidine se ems to be significantly less efficacious in elevating Ca++ than in dec reasing cAMP.