PT  - JOURNAL ARTICLE
AU  - Selvi C. Jeyaraj
AU  - Maqsood A. Chotani
AU  - Srabani Mitra
AU  - Herbert E. Gregg
AU  - Nicholas A. Flavahan
AU  - Keith J. Morrison
TI  - Cooling Evokes Redistribution of α<sub>2C</sub>-Adrenoceptors from Golgi to Plasma Membrane in Transfected Human Embryonic Kidney 293 Cells
AID  - 10.1124/mol.60.6.1195
DP  - 2001 Dec 01
TA  - Molecular Pharmacology
PG  - 1195--1200
VI  - 60
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/60/6/1195.short
4100  - http://molpharm.aspetjournals.org/content/60/6/1195.full
SO  - Mol Pharmacol2001 Dec 01; 60
AB  - Cold-induced vasoconstriction in cutaneous blood vessels is mediated by increased constrictor activity of vascular α2-adrenoceptors (α2-ARs). In mouse cutaneous arteries, α2-AR constriction at 37°C is mediated by α2A-ARs, whereas after cold exposure (28°C), α2C-ARs are no longer silent and mediate the remarkable cold-induced augmentation of α2-AR responsiveness. The goals of the present study were to develop a cell model of cutaneous thermoregulation and to determine the mechanisms underlying the thermosensitivity of α2C-ARs. Human embryonic kidney 293 cells were transiently transfected with the mouse α2A- or α2C-AR. In cells expressing α2A-ARs, UK-14,304 (5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine), an α2-AR agonist, inhibited (10 pM) and stimulated (1–10 nM) the accumulation of cAMP evoked by forskolin. Similar responses were obtained at 37°C and 28°C. In contrast, in cells expressing α2C-ARs, UK-14,304 did not affect forskolin-stimulated cAMP accumulation at 37°C but did cause a concentration-dependent inhibitory effect at 28°C. Subcellular fractionation revealed that at 37°C α2C-ARs were localized predominantly to Golgi compartments, whereas α2A-ARs localized predominantly to the plasma membrane. After cooling (28°C), α2C-ARs relocated from Golgi compartments to the plasma membrane, whereas the α2A-AR remained at the plasma membrane. Immunofluorescence microscopy confirmed that, at 37°C, α2A-ARs were localized to the cell surface, whereas α2C-ARs colocalized with a trans-Golgi marker. Cooling did not affect localization of α2A-ARs, but shifted α2C-ARs to the cell surface. Moderate cooling, therefore, caused a selective redistribution of α2C-ARs from the Golgi compartments to the cell surface, allowing the rescue of the α2C-adrenergic functional response. This mechanism may explain the role of α2-ARs in thermoregulation of the cutaneous circulation.