Alpha2B-adrenoceptors couple to Ca2+ increase in both endogenous and recombinant expression systems.
The ability of cloned human alpha2B-adrenoceptors heterologously expressed in Sf9 cells and endogenous alpha2B-adrenoceptors in NG 108-15 neuroblastoma x glioma cells to couple to increase of intracellular Ca2+ was studied. Ca2+ increases in NG 108-15 cells were detectable but slight, whereas those in alpha2B-adrenoceptor-expressing Sf9 cells were greater. In the latter, the maximum Ca2+ increase correlated positively, and the EC50-value of noradrenaline negatively, with the receptor expression density. The order of potency of the agonists was D-medetomidine ([D]-4-[5]-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole) > noradrenaline approximately = clonidine > oxymetazoline, with clonidine and UK14,304 (5-bromo-N-[4,5-dihydro-1H-imidazole-2-yl]-6-quinoxalinamine) being weak partial agonists. In Sf9 cells Ca2+ increases consisted of concomitant mobilization from an intracellular store and influx of extracellular Ca2+. In these cells alpha2B-adrenoceptor stimulation also increased the inositol 1,4,5-trisphosphate mass. We conclude that alpha2B-adrenoceptors can couple to intracellular Ca2+ increases which may involve prior activation of phospholipase C.
Holmberg
C I
CI
Turku Centre for Biotechnology, University of Turku, and Department of Biochemistry and Pharmacy, Abo Akademi University, Finland.
Kukkonen
J P
JP
Bischoff
A
A
Näsman
J
J
Courtney
M J
MJ
Michel
M C
MC
Akerman
K E
KE
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002455:Cell Division; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D009638:Norepinephrine / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D018411:Spodoptera / Q000235:genetics; D014407:Tumor Cells, Cultured
D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D011994:Recombinant Proteins; D002118:Calcium; D009638:Norepinephrine