GPR39 signaling is stimulated by zinc ions but not by obestatin

TY - JOUR

T1 - GPR39 signaling is stimulated by zinc ions but not by obestatin

AU - Holst, Birgitte

AU - Egerod, Kristoffer L

AU - Schild, Enrico

AU - Vickers, Steve P

AU - Cheetham, Sharon

AU - Gerlach, Lars-Ole

AU - Storjohann, Laura

AU - Stidsen, Carsten E

AU - Jones, Rob

AU - Beck-Sickinger, Annette G

AU - Schwartz, Thue W

N1 - Keywords: Animals; Arrestin; CHO Cells; COS Cells; Cercopithecus aethiops; Cricetinae; Cricetulus; Cyclic AMP; DNA-Binding Proteins; Eating; Gene Expression; Genes, Reporter; Humans; Inositol Phosphates; Integrases; Kidney; Luciferases; Mice; Mice, Inbred C57BL; Peptide Hormones; Polymerase Chain Reaction; Receptors, G-Protein-Coupled; Signal Transduction; Transcription Factors; Tritium; Zinc

PY - 2006

Y1 - 2006

N2 - GPR39 is an orphan member of the ghrelin receptor family that recently was suggested to be the receptor for obestatin, a peptide derived from the ghrelin precursor. Here, we compare the effect of obestatin to the effect of Zn(2+) on signal transduction and study the effect of obestatin on food intake. Although Zn(2+) stimulated inositol phosphate turnover, cAMP production, arrestin mobilization, as well as cAMP response element-dependent and serum response element-dependent transcriptional activity in GPR39-expressing cells as opposed to mock-transfected cells, no reproducible effect was obtained with obestatin in the GPR39-expressing cells. Moreover, no specific binding of obestatin could be detected in two different types of GPR39-expressing cells using three different radioiodinated forms of obestatin. By quantitative PCR analysis, GPR39 expression was readily detected in peripheral organs such as duodenum and kidney but not in the pituitary and hypothalamus, i.e. presumed central target organs for obestatin. Obestatin had no significant and reproducible effect on acute food intake in either freely fed or fasted lean mice. It is concluded that GPR39 is probably not the obestatin receptor. In contrast, the potency and efficacy of Zn(2+) in respect of activating signaling indicates that this metal ion could be a physiologically relevant agonist or modulator of GPR39.

AB - GPR39 is an orphan member of the ghrelin receptor family that recently was suggested to be the receptor for obestatin, a peptide derived from the ghrelin precursor. Here, we compare the effect of obestatin to the effect of Zn(2+) on signal transduction and study the effect of obestatin on food intake. Although Zn(2+) stimulated inositol phosphate turnover, cAMP production, arrestin mobilization, as well as cAMP response element-dependent and serum response element-dependent transcriptional activity in GPR39-expressing cells as opposed to mock-transfected cells, no reproducible effect was obtained with obestatin in the GPR39-expressing cells. Moreover, no specific binding of obestatin could be detected in two different types of GPR39-expressing cells using three different radioiodinated forms of obestatin. By quantitative PCR analysis, GPR39 expression was readily detected in peripheral organs such as duodenum and kidney but not in the pituitary and hypothalamus, i.e. presumed central target organs for obestatin. Obestatin had no significant and reproducible effect on acute food intake in either freely fed or fasted lean mice. It is concluded that GPR39 is probably not the obestatin receptor. In contrast, the potency and efficacy of Zn(2+) in respect of activating signaling indicates that this metal ion could be a physiologically relevant agonist or modulator of GPR39.

U2 - 10.1210/en.2006-0933

DO - 10.1210/en.2006-0933

M3 - Journal article

C2 - 16959833

SN - 0013-7227

VL - 148

SP - 13

EP - 20

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 1

ER -