Mohanan Valiya Veettil, Khan Reas, Paulose C S
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin-682 022, Kerala, India.
Life Sci. 2006 Feb 28;78(14):1603-9. doi: 10.1016/j.lfs.2005.07.027. Epub 2005 Oct 25.
5-HT receptors are predominantly located in the brain and are involved in pancreatic function and cell proliferation through sympathetic nervous system. The objective of this study was to investigate the role of hypothalamic 5-HT, 5-HT1A and 5-HT2C receptor binding and gene expression in rat model of pancreatic regeneration using 60% pancreatectomy. The pancreatic regeneration was evaluated by 5-HT content, 5-HT1A and 5-HT2C receptor gene expression in the hypothalamus of sham operated, 72 h and 7 days pancreatectomised rats. 5-HT content was quantified by HPLC. 5-HT1A receptor assay was done by using specific agonist [3H]8-OH DPAT. 5-HT2C receptor assay was done by using specific antagonist [3H]mesulergine. The expression of 5-HT1A and 5-HT2C receptor gene was analyzed by RT-PCR. 5-HT content was higher in the hypothalamus of 72 h pancreatectomised rats. 5-HT1A and 5-HT2C receptors were down-regulated in the hypothalamus. RT-PCR analysis revealed decreased 5-HT1A and 5-HT2C receptor mRNA expression. The 5-HT1A and 5-HT2C receptors gene expression in the 7 days pancreatectomised rats reversed to near sham level. This study is the first to identify 5-HT1A and 5-HT2C receptor gene expression in the hypothalamus during pancreatic regeneration in rats. Our results suggest the hypothalamic serotonergic receptor functional regulation during pancreatic regeneration.
5-羟色胺(5-HT)受体主要位于大脑中,并通过交感神经系统参与胰腺功能和细胞增殖。本研究的目的是利用60%胰腺切除术的大鼠模型,探讨下丘脑5-HT、5-HT1A和5-HT2C受体结合及基因表达在胰腺再生中的作用。通过假手术、胰腺切除术后72小时和7天的大鼠下丘脑5-HT含量、5-HT1A和5-HT2C受体基因表达来评估胰腺再生情况。5-HT含量通过高效液相色谱法(HPLC)进行定量。5-HT1A受体测定采用特异性激动剂[3H]8-羟基二丙胺([3H]8-OH DPAT)进行。5-HT2C受体测定采用特异性拮抗剂[3H]美舒麦角([3H]mesulergine)进行。5-HT1A和5-HT2C受体基因的表达通过逆转录-聚合酶链反应(RT-PCR)进行分析。胰腺切除术后72小时的大鼠下丘脑5-HT含量较高。下丘脑5-HT1A和5-HT2C受体下调。RT-PCR分析显示5-HT1A和5-HT2C受体mRNA表达降低。胰腺切除术后7天的大鼠5-HT1A和5-HT2C受体基因表达恢复至接近假手术水平。本研究首次鉴定了大鼠胰腺再生过程中下丘脑5-HT1A和5-HT2C受体基因的表达。我们的结果提示了胰腺再生过程中下丘脑血清素能受体的功能调节。