Back to Search Start Over

Neuropeptide Y Treatment and Food Deprivation Increase Cyclic AMP Response Element-Binding in Rat Hypothalamus

Authors :
Ambikaipakan Balasubramaniam
Josef E. Fischer
Sulaiman Sheriff
William T. Chance
Source :
Molecular Pharmacology. 51:597-604
Publication Year :
1997
Publisher :
American Society for Pharmacology & Experimental Therapeutics (ASPET), 1997.

Abstract

Intrahypothalamic (IHT) administration of neuropeptide Y (NPY) induces a robust feeding response in rats. We have shown previously that NPY-induced feeding is mediated by a pertussis-toxin-sensitive G protein in rats. NPY receptors are coupled to cAMP and Ca2+. Because these second messengers are known to activate cAMP response element binding proteins, (CREB), cAMP response element modulators, or activating transcription factor 1, we investigated the involvement of these transcription factors in NPY-induced feeding in rats. Compared with control injections of cerebrospinal fluid (1 microl), IHT administration of NPY increased cAMP response element (CRE) binding to rat hypothalamic nuclear extracts in a time-dependent manner, as detected by an electrophoretic mobility shift assay. In contrast, IHT administration of the anorectic neuropeptide, pituitary adenylate cyclase activating polypeptide, strongly inhibited the CRE binding. Food deprivation for 48 hr also increased CRE binding, whereas 8 hr of refeeding normalized CRE activity. Preincubation of the hypothalamic nuclear extracts of NPY-treated and unfed rats with antibody specific to CREB blocked CRE binding, whereas preincubation with phosphoCREB antibody retarded the migration of CRE-protein complex, indicating that phosphoCREB is involved in this process. Consistently, immunohistochemical studies with food-deprived rats showed an intense phosphoCREB signal in the paraventricular nuclei and ventromedial hypothalamus in comparison to rats fed ad libitum. Hypothalamic calcium/calmodulin-dependent protein kinase II activity was also increased by IHT-NPY. These results suggest that calcium/calmodulin-dependent protein kinase II induced phosphorylation of CREB may be involved in regulating feeding behavior induced by NPY.

Details

ISSN :
15210111 and 0026895X
Volume :
51
Database :
OpenAIRE
Journal :
Molecular Pharmacology
Accession number :
edsair.doi.dedup.....e55f0e4e17de26bc8619863974ead4e6
Full Text :
https://doi.org/10.1124/mol.51.4.597