Galanin, a 29 amino-acid peptide, was originally isolated from porcine intestine. Crit Rev Neurobiol. 1993;7(3-4):229-74.  and has been shown to have orexigenic properties. Galanin is synthesized from a large precursor peptide the pre-pro-Galanin. Galanin-like immunoreactivity is widely distributed and is  found in medium eminence, hypothalamus, and arcuate nucleus where it functions as  a neurotransmitter. 

Galanin has been localized in reproductive tissues and this suggests that it may play an oestrogen mediated role in the hypothalamic and pituitary function. Oestrogen significantly increases the synthesis of Galanin mRNA and the Galanin peptide in the rat pituitary   with a 30 fold rise in pituitary levels during the oestrous cycle in rats. Galanin has been demonstrated in the placenta and levels in the pituitary rise in pregnancy.   Endocrinology. 1992 Jan;130(1):458-64.   Thyroid hormones seem to have a permissive role in Galanin expression and might be related to Galanin mediating the secretion of TSH from the pituitary.  Proc Natl Acad Sci U S A. 1988 Dec;85(24):9861-5.   Other areas of documented Galanin expression include human adrenals, and tumours including pituitary adenomas Acta Physiol Scand. 1989 Dec;137(4):561-2 and phaeochromocytoma. J Clin Endocrinol Metab. 1986 Dec;63(6):1372-8.    Galanin coexists with other neuropeptides in the brain including GABA, dynorphin, cholecystokinin, noradrenaline, 5-hydroxytryptamine (5-HT), NPY and Neurotensin  Brain Res. 1986 Jun;396(2):97-155.  as well as the hormone LHRH.  Two endogenously occurring Galanin receptor agonists [Galanin (7-29) and Galanin 9-29) ]have been described from the porcine adrenals.  J Clin Endocrinol Metab. 1986 Dec;63(6):1372-8  Three G protein coupled Galanin receptor subtypes (GalR1-GalR3) have been cloned . Trends Pharmacol Sci. 2000 Mar;21(3):109-17

Actions

Intraventricular administration of Galanin (pGal) in the rat stimulates food intake, J Neurosci. 1990 Nov;10(11):3695-700.  specifically the ingestion of fat. Brain Res. 1992 Dec 18;599(1):148-52.  Galanin-induced feeding was less marked than NPY-induced feeding, and shorter lasting for about 30 minutes. Galanin antagonists have been shown to attenuate Galanin induced feeding. Eur J Neurosci. 1993 Nov 1;5(11):1528-33.   Infusion of Galanin anti-sense oligonucleotides in the PVN inhibit feeding.  Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10375-9.
Galanin injection inhibits glucose induced insulin release from mouse pancreatic islets. Regul Pept. 1995 Aug 22;58(3):135-9.   Intravenous infusion of Galanin in humans induce  hyperglycaemia and glucose intolerance and inhibits the secretion of  insulin, somatostatin and pancreatic polypeptide from the pancreas.      Galanin also increases plasma growth hormone and prolactin levels and decreases dopamine levels in the median eminence.

Mechanism of action

NPY producing neurons are in direct communication with Galanin producing neurons in the ARC and PVN. Endocrinology. 1996 Jul;137(7):3069-78.   This may suggest a mediation of NPY action by Galanin. Galanin positive nerve terminals have synaptic links with the POMC containing dendrites in the ARC. Naloxone, an opiate receptor antagonist, decreases Galanin induced feeding, Physiol Behav. 1994 Oct;56(4):811-3.  which would be in keeping with the possibility of mediation of galanin's  action through β-endorphin release, J Neuroendocrinol. 1995 Aug;7(8):579-88.  over and above the direct mediation through Galanin receptors in the hypothalamus. Nor-epinephrine release by Galanin neurons in the PVN has also been suggested as a possible mechanism of Galanin's action on feeding stimulation.

Physiological Role

Several Galanin receptor antagonists have been synthesised which show high affinity for the Galanin receptor making an in vivo pharmacological use feasible.  Receptor antagonists with tissue specific receptor affinities are available which distinguish between pancreatic and CNS Galanin receptors.  Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11287-91.  While Galanin receptor antagonist inhibits Galanin induced feeding, Eur J Neurosci. 1993 Nov 1;5(11):1528-33     normal feeding was not suppressed by Galanin receptor antagonists, Am J Physiol. 1995 Sep;269(3 Pt 2):R511-8  questioning the physiological role of Galanin in normal feeding behaviour. Further, increased appetite evoked by fasting is not associated with increased Galanin gene expression in the ARC,  Brain Res Bull. 1993;31(3-4):361-7  but in fact a reduction in Galanin gene expression. Neuroendocrinology. 1990 Nov;52(5):441-7.   Thus clarification of Galanin's role in the physiology of normal  feeding is needed which might be made possible by the use of antagonists, although their use is limited by decreased passage through blood brain barrier and  demonstration of agonistic activity at higher doses.  Galanin facilitates hyperglycaemia as demonstrated by suppression of insulin secretion from the pancreas, Regul Pept. 1995 Aug 22;58(3):135-9.   probably mediated through noradrenaline which coexists with Galanin in the sympathetic nerves innervating the pancreas. Acta Physiol Scand. 1991 Oct;143(2):145-52.    and thus could contribute to the development of stress hyperglycaemia.

Galanin is a physiological antagonist of substance P and a reduction of pain sensation has been demonstrated on intrathecal application.  Acta Physiol Scand. 1989 Nov;137(3):463-4.  Galanin may also be involved in cognitive performance. Intracerebroventricular injection of Galanin decreases cognitive performance,   Eur J Pharmacol. 1988 Feb 9;146(2-3):327-9.    while Galanin antagonist (M35) improves maze performance in rats. Neuroscience. 1992 Nov;51(1):1-5. Galanin also seems to exert anti-oxidative properties and may be of use in preventing anoxic damage by inhibition of release of excitatory amino acids in the hypothalamus.  Eur J Pharmacol. 1993 Mar 15;245(1):1-7.

Galanin Like Peptide  (GALP)

Galanin-like peptide (GALP) is a  60 amino acid peptide produced in the hypothalamic arcuate nucleus (ARC). J Biol Chem. 1999 Dec 24;274(52):37041-5.   As the name implies, it is at least partially structurally homologous to Galanin. GALP demonstrates affinity for both GalR1 and GalR2 receptors with higher affinity for GalR2.  J Biol Chem. 1999 Dec 24;274(52):37041-5.  The orexigenic activity of GALP may be mediated through GalR1 receptors.   FEBS Lett. 1998 Sep 4;434(3):277-82.    GALP may well have other as yet unidentified receptors mediating its effects on feeding, as evidenced by GALP induced c-Fos expression in the internal zone of the median eminence without the expression of Galanin receptors.   Endocrinology. 2003 Apr;144(4):1143-6. In contrast to Galanin, GALP distribution is mostly restricted to the arcuate nucleus in the hypothalamus. Neuroendocrinology. 2000 Aug;72(2):67-71.  and to the median eminence Neuroreport. 2000 Nov 27;11(17):3909-13.   and pituitary gland to a degree.   Fasting for forty eight hours reduces plasma GALP levels.   Neuroendocrinology. 2001 Dec;74(6):423-32.  GALP mRNA levels are reduced in the hypothalamus of Zucker obese rats (rats with leptin receptor mutation), db/db rats and  ob/ob mice (mice with leptin deficiency).  In leptin deficient ob/ob mice, leptin administration increases GALP mRNA expression. Endocrinology. 2003 Jun;144(6):2634-43.   GALP cells in the arcuate nucleus co-express the leptin receptor Ob-Rb. Endocrinology. 2001 Apr;142(4):1626-34.   GALP gene expression in the arcuate nucleus in rat is reduced by fasting although Leptin administration reverses this reduction suggesting a possible role for Leptin in the regulation of galanin's effects on energy balance. Endocrinology. 2000 Jul;141(7):2703-6  

Injection of GALP into the lateral ventricle produces c-fos activation in the supraoptic nucleus, the dorsomedial nucleus of the hypothalamus, the lateral hypothalamus, and the nucleus of tractus solitarius, and the ARC. Endocrinology. 2003 Sep;144(9):3977-84.  although neuronal activation varies depending on the site of GALP injection. Endocrinology. 2003 Apr;144(4):1143-6.

GALP regulates plasma (LH) levels via the activation of gonadotropin-releasing hormone (GnRH)-producing neurons. GALP may also be involved in the regulation of ADH as evidenced from GALP mRNA up regulation in the posterior pituitary by salt loading and dehydration in pituicytes. Neuroendocrinology. 2001 Jan;73(1):2-11

In conclusion, Galanin or its antagonists may have a role in the future in the pharmacotherapy of pain, Alzheimer's, neuroendocrine secretion regulation as in pituitary tumours, limiting oxidative damage, as well as in the treatment of  obesity.

  .

    This page was last updated on: 07/03/2007

 Copyright and Terms of use