Bedecs K, Berthold M, Bartfai T
Department of Neurochemistry and Neurotoxicology, Arrhenius Laboratories of Natural Sciences, Stockholm University, Sweden.
Int J Biochem Cell Biol. 1995 Apr;27(4):337-49. doi: 10.1016/1357-2725(95)00008-d.
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 Gly1, Trp2, Asn5 and Tyr9, 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 Gi-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 Ca2+ 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.
甘丙肽是一种由29/30个氨基酸组成的神经肽，不属于任何已知的肽家族。该分子N端的前16个氨基酸对于受体识别和受体激活而言既必要又充分。甘丙肽在中枢和胰腺作用中的主要药效基团分别是Gly1、Trp2、Asn5和Tyr9。神经肽甘丙肽在中枢和外周神经系统中均有多种作用。在中枢，甘丙肽强烈刺激脂肪摄取并损害认知能力。甘丙肽可抑制海马体中缺氧时谷氨酸的释放，并且甘丙肽在蓝斑核中的超极化作用会影响大脑中的去甲肾上腺素能紧张度。在脊髓中，甘丙肽抑制脊髓兴奋性并增强吗啡的镇痛作用。在神经内分泌系统中，甘丙肽以刺激方式作用于生长激素和催乳素的释放，而在周围组织中，甘丙肽抑制葡萄糖诱导的胰岛素释放。甘丙肽还会引起空肠收缩。甘丙肽受体是一种与Gi蛋白偶联的膜结合糖蛋白，估计分子量为53 kDa。基于药理学依据已提出了几种假定的组织特异性甘丙肽受体亚型。甘丙肽受体和甘丙肽样免疫反应性在中枢神经系统中的分布相互重叠，在蓝斑核、中缝核和下丘脑等区域两者含量都很高。甘丙肽受体激活会导致细胞内Ca(2+)浓度降低，这要么是通过直接作用于电压敏感Ca(2+)通道，要么是通过打开K(+)通道或抑制腺苷酸环化酶活性间接实现。细胞内Ca2+水平降低随后会导致磷脂酶C（PLC）活性降低。甘丙肽还抑制去极化诱导的环鸟苷酸（cGMP）合成。最近开发了许多肽类合成高亲和力甘丙肽受体拮抗剂，这使得人们能够阐明内源性甘丙肽在多个系统中的功能作用。此外，通过使用这些新的甘丙肽受体配体可以区分甘丙肽受体的假定亚型。
