Jp. Kukkonen et al., LIGAND-SELECTIVE AND SUBTYPE-SELECTIVE COUPLING OF HUMAN ALPHA-2-ADRENOCEPTORS TO CA-HAMSTER OVARY CELLS(+ ELEVATION IN CHINESE), The Journal of pharmacology and experimental therapeutics, 287(2), 1998, pp. 667-671
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.