Activity of centrally administered galanin fragments on stimulation of feeding behavior and on galanin receptor binding in the rat hypothalamus

Abstract

Synthetic fragments of galanin 1-29 were administered intraventricularly or into the paraventricular nucleus of the hypothalamus for analysis of the critical amino acid sequence necessary to stimulate feeding behavior in rats. Galanin 1-29 and galanin fragment 1-16 significantly increased feeding at doses of 6 nmol microinjected into the lateral ventricles and 1 nmol microinjected into the hypothalamus. There was no significant effect of D-TRP2 galanin 1-16 microinjected into the hypothalamus, and no significant effect of galanin fragments 1-9, 10-20, 12-29, 17-29, or 21-29 microinjected intraventricularly, on food consumption. Synthetic fragments of galanin 1-29 were assayed for displacement of 125I-galanin 1-29 binding to rat hypothalamic membranes. The efficacies of the galanin fragments in the feeding paradigm were consistent with the relative affinities of these fragments for the hypothalamic galanin receptor in equilibrium binding experiments. The first 16 N-terminal amino acids appear to contain galanin agonist activity on increasing food consumption and to bind to the galanin receptor in the rat hypothalamus.

Central nervous system regulation of food intake and energy expenditure: role of galanin-mediated feeding behavior

“…In mammals, acute injection of galanin or active fragments such as galanin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), into the PVN, lateral and ventromedial hypothalamic nuclei, and the central nucleus of the amygdala, significantly increases food intake and produces rapid increases in the feeding response and total caloric intake [4,5,11,12] . The effects of galanin on feeding be-…”

Molecular Characterization and Expression of Cloned Human Galanin Receptors GALR2 and GALR3

“…Galanin's proposed role with respect to satiety is the demonstration that it increases food intake in rodents with a preference for fat diets (Tempel et al, 1988). It is interesting that central administration of neuropeptide Y, another proposed mediator of body weight homeostasis, up-regulates galanin concentrations, potentially augmenting galanin's stimulation of food intake (Crawley et al, 1990). Galanin peptide antagonists have been shown to be effective in blocking galanin' s promotion of food intake (Crawley et al, 1993).…”

Galanin-receptor ligand M40 peptide distinguishes between putative galanin-receptor subtypes.

“…It is a potent inhibitor of glucose-induced insulin release (2), it inhibits hippocampal acetylcholine release (3) induced by systemic administration of scopolamine (4), it impairs cognitive performance (5, 6), it stimulates feeding behavior upon hypothalamic or intracerebroventricular injection (7,8), it stimulates growth hormone secretion (9), and it has a biphasic effect on the spinal flexor reflex (10). Galanin hyperpolarizes noradrenergic cell bodies in the locus coeruleus (11) Accordingly, a galanin-receptor subtype has been suggested, which is composed of nervous tissue and pancreatic galanin receptors that recognize the N-terminal 1-to 15-aa or 1-to 16-aa fragment of galanin as high-affinity agonists, whereas another putative galanin-receptor subtype in smooth muscle requires both the N and C terminus of galanin for binding and biological action (25).…”

“…It is a potent inhibitor of glucose-induced insulin release (2), it inhibits hippocampal acetylcholine release (3) induced by systemic administration of scopolamine (4), it impairs cognitive performance (5, 6), it stimulates feeding behavior upon hypothalamic or intracerebroventricular injection (7,8), it stimulates growth hormone secretion (9), and it has a biphasic effect on the spinal flexor reflex (10). Galanin hyperpolarizes noradrenergic cell bodies in the locus coeruleus (11) and inhibits the release of glutamate, but not of raminobutyric acid, in the hippocampus (12).…”