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Localization of neuropeptide Y receptor Y5 mRNA in the guinea pig brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
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2004 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 117, 61-67 p.Article in journal (Refereed) Published
Abstract [en]

Neuropeptide Y (NPY) has prominent stimulatory effects on food intake in virtually all animals that have been studied. In mammals, the effect is primarily mediated by receptors Y1 and Y5, which seem to contribute to different aspects of feeding behavior in guinea pigs and rats/mice. Interestingly, differences in receptor distribution among mammalian species have been reported. To get a broader perspective on the role of Y5, we describe here studies of guinea pig (Cavia porcellus), a species which due to its phylogenetic position in the mammalian radiation is an interesting complement to previous studies in rat and mouse. Guinea pig brain sections were hybridized with two 35S-labeled oligonucleotides complementary to Y5 mRNA. The highest expression levels of Y5 mRNA were observed in the hippocampus and several hypothalamic and brain stem nuclei implicated in the regulation of feeding, such as the paraventricular, arcuate and ventromedial hypothalamic nuclei. This contrasts with autoradiography studies that detected low Y5-like binding in these areas, a discrepancy observed also in rat and human. Y5 mRNA expression was also seen in the striatum, in great contrast to mouse and rat. Taken together, these data show that Y5 mRNA distribution displays some interesting species differences, but that its expression in feeding centers seems to be essentially conserved among mammals, adding further support for an important role in food intake.

Place, publisher, year, edition, pages
2004. Vol. 117, 61-67 p.
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-89539DOI: 10.1016/j.regpep.2003.10.010OAI: oai:DiVA.org:uu-89539DiVA: diva2:161091
Available from: 2001-11-01 Created: 2001-11-01 Last updated: 2013-01-07Bibliographically approved
In thesis
1. Neuropeptide Y Receptors in Human, Guinea pig and Chicken: Cloning, in vitro Pharmacology and in situ Hybridization
Open this publication in new window or tab >>Neuropeptide Y Receptors in Human, Guinea pig and Chicken: Cloning, in vitro Pharmacology and in situ Hybridization
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neuropeptide Y (NPY) is known to influence a vast number of physiological and behavioral processes such as vasoconstriction, circadian rhythms, feeding, anxiety and memory. Peptides of the NPY family bind to five different cloned G-protein coupled receptor subtypes (Y1, 2, 4-6). The studies compiled in this thesis present inter-species comparisons of sequence similarities, binding properties and expression patterns among receptors of the NPY family.

Cloning of Y1 and Y2 receptor subtypes from guinea pigs revealed strong binding profile similarity to the corresponding human receptors. Previously demonstrated atypical binding profiles in the caval vein of guinea pigs were concluded to result from other receptors than the cloned Y1 and Y2 receptors, or possibly combinations of distinct receptor subtypes.

The guinea pig Y5 receptor was found to be expressed in regions of the brain that have been indicated as important for regulation of food intake. Expression in the hypothalamus, amygdala and brain stem was noticed, similar to studies in rats and humans. In other brain regions, such as the striatum and hippocampus, some species differences were observed.

Mutagenesis studies of the human Y1 receptor indicated sites important for binding both of endogenous agonists and synthetic antagonists. Putative new sites of interaction with the Y1 antagonists BIBP3226 and/or SR120819A were recognized. The data were used to construct a three-dimensional structure model, based on a high-resolution bovine rhodopsin model.

Cloning of the chicken (Gallus gallus) Y1, Y2 and Y5 receptors revealed high sequence similarities with mammalian receptors. Most endogenous ligands bound with similar affinities as to mammalian receptors. The strongest exception was the discovery of high-affinity binding to chicken Y2 of [Leu31, Pro34]NPY, which was previously considered to bind non-Y2 receptors only.

The new human Y1 receptor model provides a basis for further investigations of ligand-receptor interactions which will be aided by information on NPY receptors from other taxa. Guinea pigs are concluded to be a good complement to rats and mice for studying NPY signaling. These results demonstrate the benefits of species comparisons for pharmacological studies.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2001. 55 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1097
Neurosciences, G-protein coupled receptor, neuropeptide Y, neuropeptide Y receptor, ortholog, chicken, guinea pig, mutagenesis, receptor computer modeling, mRNA in situ hybridization, Neurovetenskap
National Category
Research subject
Medical Pharmacology
urn:nbn:se:uu:diva-1502 (URN)91-554-5160-8 (ISBN)
Public defence
2001-11-23, lecture hall B41, Biomedical Centre, Uppsala, 09:15
Available from: 2001-11-01 Created: 2001-11-01Bibliographically approved

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Bergqvist, ChristinaKällström, LillemorLarhammar, Dan
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