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Neuropeptide Y Treatment and Food Deprivation Increase Cyclic AMP Response Element-Binding in Rat Hypothalamus
- 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.
- Subjects :
- Male
medicine.medical_specialty
G protein
Response element
Hypothalamus
Appetite Stimulants
Neuropeptide
CREB
Rats, Sprague-Dawley
Internal medicine
medicine
Animals
Neuropeptide Y
Phosphorylation
Cyclic AMP Response Element-Binding Protein
CAMP response element binding
Cell Nucleus
Pharmacology
Neurotransmitter Agents
biology
Drug Administration Routes
Neuropeptides
Neuropeptide Y receptor
Rats
Endocrinology
Calcium-Calmodulin-Dependent Protein Kinases
Second messenger system
biology.protein
Pituitary Adenylate Cyclase-Activating Polypeptide
Molecular Medicine
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Food Deprivation
Protein Binding
Subjects
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