Hypothalamic 5-HT functional regulation through 5-HT1A and 5-HT2C receptors during pancreatic regeneration

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-HT1(A) and 5-HT2(C) receptor binding and gene expression in rat model of pancreatic regeneration using 60% pancreatectomy. The pancreatic regeneration was evaluated by 5-HT content, 5-HT1(A) and 5-HT2(C) receptor gene expression in the hypothalamus of sham operated, 72 h and 7 days pancreatectomised rats. 5-HT content was quantified by HPLC. 5-HT1(A) receptor assay was done by using specific agonist [H-3]8-OH DPAT. 5-HT2(C) receptor assay was done by using specific antagonist [H-3]mesuler-ine. The expression of 5-HT1(A) and 5-HT2(C) receptor gene was analyzed by RT-PCR. 5-HT content was higher in the hypothalamus of 72 h pancreatectomised rats. 5-HT1(A) and 5-HT2(C) receptors were down-regulated in the hypothalamus. RT-PCR analysis revealed decreased 5-HT1(A) and 5-HT2(C) receptor mRNA expression. The 5-HT1(A) and 5-HT2(C) receptors gene expression in the 7 days pancreatectomised rats reversed to near sham level. This study is the first to identify 5-HT1(A) and 5-HT2(C) receptor gene expression in the hypothalamus during pancreatic regeneration in rats. Our results suggest the hypothalamic serotonergic receptor functional regulation during pancreatic regeneration. (c) 2005 Elsevier Inc. All rights reserved.