Ligand- and subtype-selective coupling of human alpha-2 adrenoceptors to Ca++ elevation in Chinese hamster ovary cells.
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-([17beta]-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.
Kukkonen
J P
JP
Department of Physiology, Uppsala University, Uppsala, Sweden.
Renvaktar
A
A
Shariatmadari
R
R
Akerman
K E
KE
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D011994:Recombinant Proteins; D000242:Cyclic AMP; D002118:Calcium