Smith R G, Griffin P R, Xu Y, Smith A G, Liu K, Calacay J, Feighner S D, Pong C, Leong D, Pomés A, Cheng K, Van der Ploeg L H, Howard A D, Schaeffer J, Leonard R J
Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, USA.
Biochem Biophys Res Commun. 2000 Oct 5;276(3):1306-13. doi: 10.1006/bbrc.2000.3610.
The growth hormone secretagogue receptor (GHS-R) is involved in the regulation of pulsatile GH release. However, until recently, natural endogenous ligands for the receptor were unknown. We fractionated porcine hypothalamic extracts and assayed fractions for activity on HEK293 cells expressing GHS-R and aequorin. A partial agonist was isolated and identified using microspray tandem mass spectrometry as adenosine. GHS-R activation by adenosine and synthetic adenosine agonists is inhibited by the GHS-R selective antagonists L-765,867, D-Lys(3)-GHRP-6, and by theophylline and XAC. Cross desensitization of the GHS-R occurs with both MK-0677 and adenosine. Ligand binding and site directed mutagenesis studies show that adenosine binds to a binding site that is distinct from the previously characterized MK-0677 and GHRP-6 binding pocket. We propose, that adenosine is a physiologically important endogenous GHS-R ligand and speculate that GHS-R ligands modulate dopamine release from hypothalamic neurons.
生长激素促分泌素受体（GHS-R）参与脉冲式生长激素释放的调节。然而，直到最近，该受体的天然内源性配体仍不为人知。我们对猪下丘脑提取物进行分级分离，并检测各分级对表达GHS-R和水母发光蛋白的HEK293细胞的活性。分离出一种部分激动剂，并通过微喷雾串联质谱鉴定为腺苷。GHS-R选择性拮抗剂L-765,867、D-Lys(3)-GHRP-6、茶碱和XAC可抑制腺苷及合成腺苷激动剂对GHS-R的激活。GHS-R与MK-0677和腺苷均会发生交叉脱敏。配体结合和定点诱变研究表明，腺苷结合的位点与先前鉴定的MK-0677和GHRP-6结合口袋不同。我们认为，腺苷是一种具有重要生理意义的内源性GHS-R配体，并推测GHS-R配体可调节下丘脑神经元释放多巴胺。
