RT Journal Article
SR Electronic
T1 Ligand- and Subtype-Selective Coupling of Human<em>Alpha</em>-2 Adrenoceptors to Ca<sup>++</sup> elevation in Chinese Hamster  Ovary Cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 667
OP 671
VO 287
IS 2
A1 Jyrki P. Kukkonen
A1 Annika Renvaktar
A1 Ramin Shariatmadari
A1 Karl E. O. Åkerman
YR 1998
UL http://jpet.aspetjournals.org/content/287/2/667.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics