Endocrine Abstracts (2001) 2 OC17

The novel hypothalamic peptide Galanin-Like Peptide (GALP) stimulates food intake in male wistar rats

A Seth, SA Stanley, W Dhillo, KG Murphy, MA Ghatei & SR Bloom

Department of Metabolic Medicine, Imperial College School of Medicine, Hammersmith Hospital, London, UK.

Galainin-like peptide (GALP) is a recently identified hypothalamic neuropeptide expressed in the arcuate nucleus. It is structurally related to galanin, GALP amino acid residues 9-21 are identical to the N terminal 1-13 residues of galanin. GALP binds to galanin receptors with high affinity but has greatest affinity to the GAL R2 receptor. Galanin has previously been demonstrated to significantly increase food intake when administered into the third ventricle or the paraventricular nucleus (PVN) of rats. The purpose of this study was firstly to examine the effect of GALP on feeding behaviour and secondly to examine the central effectors of its actions.

Male Wistar rats were cannulated into the PVN. Following seven days' recovery, equimolar doses of GALP or galanin (0.03, 0.1, 0.3, 1 and 3nmol) where injected into PVN and food intake measured. Both galanin and GALP significantly increased food intake 1 hour after injection at both 1 and 3 nmol.( 1 hour food intake: saline 0.70 ± 0.21g vs Galanin (3nmol) 3.36±0.33g, p<0.001, GALP (3nmol) 4.18±0.61g, p<0.001).

The effect of GALP on other hypothalamic peptides associated with feeding behaviour was investigated using a static hypothalamic incubation system. GALP 100nM significantly increased neuropeptide Y (NPY) release (NPY release; basal 39.4 ±4.3 fmol/explant, GALP 60.10 ± 9.3 fmol/explant, p<0.01) and significantly reduced cocaine and amphetamine regulated transcript (CART) release (basal 153.63±19.99.fmol/explant, GALP 86.44±12.48 fmol/explant, p<0.01)from isolated hypothalami. In contrast, galanin had no effect on the release of NPY or CART.

In this study, we have found that GALP significantly stimulates food intake when administered into the PVN, and this effect is of a similar magnitude to that of galanin. In vitro studies suggest this feeding behaviour may be mediated by other hypothalamic neuropeptides such as NPY.

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