Psychiatry related information on GAL

• Several studies show that galanin is involved in control of pain threshold and acts synergistically with morphine, hence, inhibition of galanin degradation may be a pharmaceutical target for treatment of pain [1].

High impact information on GAL

• Identification of a TPA-responsive element mediating preferential transactivation of the galanin gene promoter in chromaffin cells [2].
• To identify its transcriptional regulatory elements, 5'-flanking sequences of the galanin gene were transiently transfected into primary cultures of bovine chromaffin cells within reporter gene constructs [2].
• The gene encoding the neuropeptide galanin is upregulated by second messenger signal transduction pathways in bovine chromaffin cells [2].
• This cis-regulatory element mediates preferential TPA stimulation of transcription from the galanin promoter in chromaffin cells compared with bovine endothelial or HeLa cells [2].
• TNF-alpha and IL-1 induced a time- and dose-dependent increase in galanin, vasoactive intestinal polypeptide, and secretogranin II mRNA levels [3].

Biological context of GAL

• A description is given of the primary structure of a bovine adrenal medullary precursor protein (123 amino acids), containing a nonrepetitive galanin sequence, different in four amino acid positions from pig galanin, structural information deduced from the nucleotide sequence analysis of two cDNA clones [4].
• GAL mRNA up-regulation via the protein kinase A (PKA) pathway (25 microM forskolin) required new protein synthesis [5].
• Cotransfection of a GAL reporter gene along with expression plasmids encoding c-Jun plus c-Fos, or the catalytic subunit of PKA (PKAbeta), resulted in a 4- to 8-fold enhancement of GAL reporter gene transcription [5].
• We investigated trans-acting factors mediating galanin (GAL) gene activation by protein kinase-dependent signal transduction pathways in chromaffin cells [5].
• Transcriptional activation required the galanin 12-O-tetradecanoylphorbol-13-acetate (phorbol-12-myristate-13-acetate) response element (GTRE) octamer sequence (TGACGCGG) in the proximal enhancer of the GAL gene, previously shown to confer phorbol ester responsiveness in chromaffin cells [5].

Anatomical context of GAL

• Mutation of the galanin promoter within the -66 to -62 region renders it unresponsive to transcriptional stimulation by TPA, and a correspondingly mutated oligonucleotide fails to bind chromaffin cell nuclear proteins in a gel-shift assay [2].
• Nucleotide sequence analysis of cDNAs encoding a bovine galanin precursor protein in the adrenal medulla and chemical isolation of bovine gut galanin [4].
• Endocrine cells showing immunoreactivity for GAL and SP were observed in the large islets and islets of Langerhans, respectively [6].
• The exocrine pancreas was shown to have an appreciable number of GAL- and SP-immunoreactive nerve fibres but few fibres showing immunoreactivity for VIP and CGRP [6].
• The neuropeptide galanin (GAL) is widely distributed throughout the diffuse neuroendocrine system, and is coexpressed with acetylcholine, norepinephrine, prolactin, and a variety of other messenger substances in different cell types [7].

Associations of GAL with chemical compounds

• Pairs of lysine and arginine residues separate the galanin sequence N-terminally from the initiating methionine and a 29 amino acid leader peptide and C-terminally from a 59 amino acid peptide [4].
• Elevated potassium stimulation of GAL mRNA was completely blocked, but pituitary adenylyl cyclase-activating polypeptide and histamine stimulations were only partially blocked, by cycloheximide [5].
• The involvement of activator protein-1(AP-1) and cAMP response element-binding protein (CREB) in serine/threonine protein kinase activation of GAL gene transcription was assessed [5].
• The regulation of GAL biosynthesis and secretion were studied by measuring changes in messenger RNA (mRNA(GAL], and peptide immunoreactivity, 24-72 h after stimulation of secretion (40 mM potassium or 10 microM veratridine), or exposure to stimulators of protein kinase C (100 nM phorbol myristate acetate) and protein kinase A (25 microM forskolin) [7].
• GH and LH responsiveness to exogenous GH-releasing hormone and gonadotropin-releasing hormone was not significantly modulated by galanin in our experimental model [8].

Other interactions of GAL

• Both inducible and constitutive activator protein-1-like transcription factors are used for transcriptional activation of the galanin gene by different first and second messenger pathways [5].
• These signals include nutrients, metabolites, reproductive hormones, stress hormones, leptin, insulin, gut peptides, cytokines, and neuropeptides such as neuropeptide Y, galanin, and corticotrophin-releasing factor [9].

Analytical, diagnostic and therapeutic context of GAL

• Northern blot analysis revealed the presence of an apparent single galanin mRNA species, of approx. 850-900 bases in size, which was present in a population of chromaffin cells scattered throughout the bovine adrenal medulla [4].
• The neurochemical code (substance P, calcitonin gene-related peptide, galanin, and neuronal nuclear protein) of labeled neurons was investigated by immunohistochemistry [10].
• The colocalization of vasoactive intestinal polypeptide (VIP) and galanin in such nitrergic neurons was also studied by means of combined histochemical and immunofluorescence techniques [11].

References