Galanin is a 29 30 amino acids long neuropeptide which does not belong to any known peptide family. The N-terminal first 16 amino acids of the molecule are both necessary and sufficient for receptor recognition and receptor activation. The main pharmacophores of galanin in its central and pancreatic actions are Gly 1 , Trp 2 , Asn 5 and Tyr 9 , respectively. The neuropeptide galanin has multiple effects in both the central and peripheral nervous systems. Centrally, galanin potently stimulates fat intake and impairs cognitive performance. Anoxic glutamate release in the hippocampus is inhibited by galanin and the noradrenergic tonus in the brain is influenced by a hyperpolarizing action of galanin in the locus coeruleus. In the spinal cord galanin inhibits spinal excitability and potentiates the analgesic effect of morphine. In the neuroendocrine system galanin acts in a stimulatory manner on the release of growth hormone and prolactin, and peripherally galanin inhibits glucose induced insulin release. Galanin also causes contraction of the jejunum. The galanin receptor is a G i -protein-coupled, membrane-bound glycoprotein with an estimated molecular mass of 53 kDa. Several putative tissue specific galanin receptor subtypes have been proposed on a pharmacological basis. The distribution of galanin receptors and of galanin like immunoreactivity are overlapping in the CNS, both being high in areas such as the locus coeruleus, raphe nucleus and hypothalamus. Galanin receptor activation leads to a reduced intracellular Ca 2+ -concentration, either by direct action on voltage sensitive Ca 2+ -channels or indirectly via opening of K + -channels or via inhibition of adenylyl cyclase activity. The lowered intracellular Ca 2+ level subsequently leads to a reduced PLC activity. Galanin also inhibits cGMP synthesis induced by depolarization. A number of synthetic high affinity galanin receptor antagonists of the peptide type were developed recently, which have enabled the elucidation of functional roles of endogenous galanin in several systems. Furthermore, putative subtypes of galanin receptors can be distinguished by the use of these new galanin receptor ligands.
The International Journal of Biochemistry & Cell Biology – Elsevier
Published: Apr 1, 1995
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