Hypothalamic Interactions Between Neuropeptide Y, Agouti‐Related Protein, Cocaine‐ and Amphetamine‐Regulated Transcript and Alpha‐Melanocyte‐Stimulating Hormone In Vitro in Male Rats

Sep 6, 2002Journal of neuroendocrinology

Interactions of hunger-related brain chemicals in the hypothalamus of male rats studied in the lab

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Abstract

Administration of 1, 10, and 100 nm of Neuropeptide Y significantly increased the release of Agrp(83-132) from hypothalamic explants.

Neuropeptide Y (NPY) and agouti-related protein (Agrp) are identified as orexigenic neuropeptides in the arcuate nucleus of the hypothalamus.
The pro-opiomelanocortin product alpha-melanocyte-stimulating hormone (alpha-MSH) is associated with reduced food intake.
Intracerebroventricular administration of cocaine- and amphetamine-regulated transcript (CART) is linked to decreased food intake, but CART appears orexigenic in specific hypothalamic areas.
Interactions among neuropeptides suggest that orexigenic neuropeptides can stimulate each other's release, indicating a potential positive-feedback loop.
The melanocortin-3 receptor in the arcuate nucleus may play a role in regulating the release of these neuropeptides.

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A number of neuropeptides implicated in the hypothalamic regulation of appetite are synthesized in the arcuate nucleus (Arc). Neuropeptide Y (NPY) and agouti-related protein (Agrp) are orexigenic. The pro-opiomelanocortin (POMC) product alpha-melanocyte-stimulating hormone (alpha-MSH) is anorectic. Intracerebroventricular administration of cocaine- and amphetamine-regulated transcript (CART) decreases food intake. However, recent results show that CART is orexigenic when injected into discrete hypothalamic nuclei. There is almost complete coexpression of NPY and Agrp mRNA in Arc neurones, and the majority of CART-containing neurones in the Arc also contain POMC mRNA. We investigated possible interactions between these neuropeptides in vitro using a rat hypothalamic explant system. Administration of 1, 10 and 100 nm of NPY to hypothalamic explants significantly increased release of Agrp(83-132)-immunoreactivity (IR). NPY (10 and 100 nm) significantly increased the release of CART(55-102)-IR and alpha-MSH-IR from hypothalamic explants. Agrp(83-132) (10 nm) administered to hypothalamic explants significantly increased the release of NPY-IR. Agrp(83-132) (10 and 100 nm) significantly decreased the release of CART(55-102)-IR from hypothalamic explants. Administration of 1, 10 and 100 nm CART(55-102) to hypothalamic explants resulted in a significant increase in NPY-IR release. Administration of 10 nm CART(55-102) to hypothalamic explants significantly increased the release of Agrp(83-132)-IR. NDP-MSH (10 nm) administered to hypothalamic explants significantly increased the release of NPY-IR. NDP-MSH (10 and 100 nm) significantly increased the release of Agrp(83-132)-IR from hypothalamic explants. These data suggest that orexigenic neuropeptides in the arcuate nucleus stimulate the release of each other, perhaps reinforcing orexigenic behaviour via a positive-feedback loop. Our results are also in keeping with the possibility that the melanocortin-3 receptor in the arcuate nucleus may influence the release of arcuate neuropeptides.

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Hypothalamic Interactions Between Neuropeptide Y, Agouti‐Related Protein, Cocaine‐ and Amphetamine‐Regulated Transcript and Alpha‐Melanocyte‐Stimulating Hormone In Vitro in Male Rats

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