Article date: December 2000
By: Petrus J Pauwels, Francis C Colpaert in Volume 131, Issue 7, pages 1385-1390
Activation of the recombinant human α2C‐adrenoceptor (α2C AR) by (−)‐adrenaline in CHO‐K1 cells transiently co‐expressing a chimeric Gαq/i1 protein induced a rapid, transient Ca2+ response with a high‐magnitude followed by a low‐magnitude phase which continued throughout the recorded time period (15 min).
Activation of the α2C AR by various α2 AR agonists revealed the following rank order of high‐magnitude Ca2+ response [Emax (%) versus 10 μM (−)‐adrenaline]: UK 14304 (102±4)=talipexole (101±3)=(−)‐adrenaline (100)=d‐medetomidine (98±1)>oxymetazoline (81±4)⋍clonidine (75±5).
The methoxy‐ (RX 821002) and ethoxy‐derivatives (RX 811059) of idazoxan and the dexefaroxan analogue atipamezole were fully effective as antagonists of both the high‐ and the low‐magnitude Ca2+ response. However, though acting as full antagonists of the high‐magnitude response, the further putative α2 AR antagonists idazoxan (27%), SKF 86466 (29%) and dexefaroxan (59%) reversed the low‐magnitude response only partially.
In conclusion, kinetic analyses of agonist : antagonist interactions at the α2C AR demonstrate a wide spectrum of partial to complete antagonism of the low‐magnitude Ca2+ response for structurally related α2 AR ligands.
Activation of the recombinant human α2C‐adrenoceptor (α2C AR) by (−)‐adrenaline in CHO‐K1 cells transiently co‐expressing a chimeric Gαq/i1 protein induced a rapid, transient Ca2+ response with a high‐magnitude followed by a low‐magnitude phase which continued throughout the recorded time period (15 min).
Activation of the α2C AR by various α2 AR agonists revealed the following rank order of high‐magnitude Ca2+ response [Emax (%) versus 10 μM (−)‐adrenaline]: UK 14304 (102±4)=talipexole (101±3)=(−)‐adrenaline (100)=d‐medetomidine (98±1)>oxymetazoline (81±4)⋍clonidine (75±5).
The methoxy‐ (RX 821002) and ethoxy‐derivatives (RX 811059) of idazoxan and the dexefaroxan analogue atipamezole were fully effective as antagonists of both the high‐ and the low‐magnitude Ca2+ response. However, though acting as full antagonists of the high‐magnitude response, the further putative α2 AR antagonists idazoxan (27%), SKF 86466 (29%) and dexefaroxan (59%) reversed the low‐magnitude response only partially.
In conclusion, kinetic analyses of agonist : antagonist interactions at the α2C AR demonstrate a wide spectrum of partial to complete antagonism of the low‐magnitude Ca2+ response for structurally related α2 AR ligands.
British Journal of Pharmacology (2000) 131, 1385–1390; doi:10.1038/sj.bjp.0703726
DOI: 10.1038/sj.bjp.0703726
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