REGULATION OF ALPHA(2)-ADRENERGIC RECEPTOR EXPRESSION AND SIGNALING IN PANCREATIC BETA-CELLS

被引:46
作者
HAMAMDZIC, D
DUZIC, E
SHERLOCK, JD
LANIER, SM
机构
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1995年 / 269卷 / 01期
关键词
ALPHA(2)-ADRENERGIC RECEPTORS; INSULIN SECRETION; RECEPTOR REGULATION; PANCREATIC BETA-CELLS;
D O I
10.1152/ajpendo.1995.269.1.E162
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Activation of alpha(2)-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 ([H-3]RX-821002) and RNA blot analysis indicate that both pancreatic beta-cell lines express the alpha(2A/D)-AR subtype [for HIT-T15 the maximum binding (B-max) = 113 +/- 28; for RIN-5AH B-max = 93 +/- 18 fmol/mg of cellular protein]. Treatment of HIT-TIS or RIN-5AH cells with glucocorticoids [dexamethasone, hydrocortisone, or prednisolone (1 mu M)] increased alpha(2)-AR mRNA level and receptor protein density three- to fivefold. 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 5'-guanylyl imidodiphosphate-sensitive binding of [H-3]UK-14304, a selective alpha(2)-AR agonist, and 2) a greater inhibition of forskolin-induced elevation of cellular adenosine 3',5'-cyclic monophosphate after receptor activation. Receptor density in HIT-T15 cells was not altered by different growth conditions, insulin (1 mu M), phorbol 12-myristate 13-acetate (1 mu M), or the sex steroids testosterone and progesterone (1 mu M). These data indicate that glucocorticoids upregulate alpha(2)-AR expression and signaling in pancreatic beta-cells. Such regulation may operate in a cell-specific manner, allowing discrete modulation of tissue responses to glucose dishomeostasis.
引用
收藏
页码:E162 / E171
页数:10
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