Regulation of [alpha]2 adrenergic receptor expression and
signalling in pancreatic [beta] cells.
Hamamdzic, Damir, Emir Duzic, John D. Sherlock, and Stephen M. Lanier.
Department of Cell and Molecular Pharmacology and Experimental
Therapeutics, Medical University of South Carolina, Charleston,
SC
APStracts 2:0035E, 1995.
Activation of alpha2-adrenergic receptors ([alpha]2-AR) in pancreatic
[beta] cells inhibits insulin secretion in response to various
stimuli and acute or long term regulation of [alpha]2-AR receptor
-mediated effects may influence the tissue response to glucose
dishomeostasis. As an initial approach to this issue we determined
the effect of various metabolic and hormonal treatments on [alpha]2
-AR expression and coupling in the pancreatic [beta] cell lines, HIT
-T15 and RIN-5AH. Radioligand binding studies ([3H]-RX821002) and RNA
blot analysis indicates that both pancreatic [beta] cell lines
express the [alpha]2A/D-AR subtype (HIT-T15 - Bmax 113 +/- 28 and
RIN-5AH Bmax = 93 +/- 18 fmol/mg of cellular protein). Treatment of
HIT-T15 or RIN-5AH cells with glucocorticoids (dexamethasone,
hydrocortisone, or prednisolone 1 uM) increased [alpha]2-AR mRNA
level and receptor protein density 3 to 5-fold. The glucocorticoid
-induced increase in receptor density in HIT-T15 cells was associated
with 1) an increase in the amount of receptors coupled to G-protein
as determined by analysis of high affinity, Gpp(NH)p-sensitive
binding of [3H]-UK14304, a selective [alpha]2-AR agonist and 2) a
greater inhibition of forskolin-induced elevation of cellular cAMP
following receptor activation. Receptor density in HIT-T15 cells was
not altered by different growth conditions, insulin (1 uM), phorbol
12-myristate 13-acetate (1 uM) or the sex steroids testosterone and
progesterone (1 uM). These data indicate that glucocorticoids
upregulate [alpha]2-AR expression and signalling in pancreatic [beta]
cells. Such regulation may operate in a cell-specific manner allowing
discrete modulation of tissue responses to glucose dishomeostasis.
Received 17 November 1994; accepted in final form 17 February
1995.
APS Manuscript Number E476-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 1 March 1995.