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Vol. 61, Issue 5, 1008-1016, May 2002
1-Adrenoceptor
Subtypes
Department of Molecular and Biomedical Pharmacology, the University
of Kentucky College of Medicine, Lexington, Kentucky (D.C., D.F.M.,
S.E.E., M.L.G., M.T.P.); and Department of Molecular and Cell
Pharmacology, National Children's Medical Research Center, Tokyo,
Japan (G.T.).
The cellular localization, agonist-mediated internalization, and
desensitization properties of the 
1-adrenoceptor
(1-AR) subtypes conjugated with green fluorescent
protein (1-AR/GFP) were assessed using real-time imaging
of living, transiently transfected human embryonic kidney (HEK) 293 cells. The 1B-AR/GFP fluorescence was detected
predominantly on the cell surface. Stimulation of the
1B-AR with phenylephrine led to an increase in
extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and
promoted rapid 1B-AR/GFP internalization. Long-term
exposure (15 h) to phenylephrine resulted in desensitization of the
1B-AR-mediated activation of ERK1/2 phosphorylation.
1A-AR/GFP fluorescence was detected not only on the cell
surface but also intracellularly. The rate of internalization of the
cell surface population 1A-AR/GFPs was slower than that
seen for the 1B-AR. Agonist exposure also resulted in
desensitization of the 1A-AR-mediated increase in ERK1/2
phosphorylation. The 1D-AR/GFP fluorescence was detected mainly intracellularly, and this localization was unaffected by exposure to phenylephrine. Phenylephrine treatment of
1D-AR/GFP expressing cells increased ERK1/2
phosphorylation. However, this increase was not significant.
Cotransfection with 
-arrestin 1 did not increase the rate or extent
of agonist-stimulated 1A- or 1B-AR/GFP
internalization. However, a dominant-negative form of the -arrestin
1, -arrestin 1 (319-418), blocked agonist-mediated internalization
of both the 1A- and 1B-ARs. These data
show that transfected 1-AR/GFP fusion proteins are
functional, that there are differences in the cellular distribution and
agonist-mediated internalization between the 1-ARs, and
that agonist-mediated 1-AR internalization is dependent
on arrestins and can be desensitized by long-term exposure to an
agonist. These differences could contribute to the diversity in
physiologic responses regulated by the 1-ARs.
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