Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) is an important hypothalamic regulator of feeding behavior. In this study we have investigated the regulation of the expression of preproNPY mRNA in male obese and lean Zucker rats by in situ hybridization. These animals represent a model of genetic obesity with hyperphagia, hyperinsulinemia and altered endocrine functions. Obese Zucker rats, treated for 12 days with 0.9% saline, had about 210% higher level of basal preproNPY mRNA expression in the arcuate nucleus when compared to their lean littermate controls. Repeated administrations of 8-hydroxy-dipropylaminotetralin (8-OH-DPAT), a serotonergic 5-HT1A agonist, or mifepristone, a glucocorticoid receptor antagonist, did not modify the basal expression of preproNPY mRNA in the Zucker phenotypes. The 8-OH-DPAT treatment significantly reduced hyperinsulinemia in obese Zucker rats without changing plasma glucose levels. The mifepristone treatment significantly increased plasma corticosterone levels in lean animals, but not in obese animals. The present study demonstrates enhanced expression of preproNPY mRNA in the arcuate nucleus in obese Zucker rats suggesting an involvement of NPY in the pathophysiology of the hyperphagic syndrome and genetically determined obesity in Zucker rats. Neither the antagonism of glucocorticoid receptors by mifepristone, nor repeated treatment with 8-OH-DPAT resulting in reduced insulin levels in obese Zucker rats, modified the basal expression of preproNPY mRNA in the arcuate nucleus.
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PMID:Effects of repeated administration of mifepristone and 8-OH-DPAT on expression of preproneuropeptide Y mRNA in the arcuate nucleus of obese Zucker rats. 165 93

Changes in glycemia and insulinemia were determined in conscious lean (FA/?) and obese (fa/fa) rats after acute administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The intravenous injection of a low dose of 8-OH-DPAT (150 micrograms/kg) to lean rats rapidly promoted hyperglycemia. This modification was associated with a slight increase in insulinemia. The injection of 8-OH-DPAT markedly decreased basal hyperinsulinemia in obese rats while inducing hyperglycemia. Further evidence of the strong inhibitory effect of 8-OH-DPAT on insulin release was obtained in lean and obese rats during glucose tolerance tests. Intracerebroventricular injection of 8-OH-DPAT (45 micrograms/animal) triggered hyperglycemia and markedly decreased insulinemia in both lean and obese rats. This hypoinsulinemic effect of 8-OH-DPAT was more pronounced in the obese than in the lean animals. Measurement of the food intake elicited by 8-OH-DPAT (500 micrograms/kg s.c.) showed that the hyperphagic action of the 5-HT1A agonist was the same in FA/? and fa/fa rats. It is suggested that: (i) hyperinsulinemia of the genetically obese rat may be diminished by a low dose of 8-OH-DPAT; (ii) 5-HT1A autoreceptor-mediated regulation of serotonergic activity is not different in lean (FA/?) and obese (fa/fa) rats; (iii) 8-OH-DPAT could be of potential therapeutic use for some aspects of the pathology of type II diabetes.
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PMID:Hyperinsulinemia of the genetically obese (fa/fa) rat is decreased by a low dose of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 296 89