Disease relevance of GAL

• The inhibitory effect of pertussis toxin on the GAL binding considers a G-protein-involved allosteric system, important for the clarification of essential steps in the G-protein-related signal transduction [1].
• It may be suggested that GAL modulates the slow, long-lasting membrane depolarization of the principal ganglion cells caused by SP in the primary afferents related to the IMG [2].
• The co-localization of GAL and dopamine beta-hydroxylase (D beta H--a key enzyme of the noradrenaline synthesis pathway) in perivascular nerve fibers could lead to considerable vasospasms in the pancreas, resulting in deeper hypoxia of the organ [3].
• Fluorescence correlation spectroscopy detects galanin receptor diversity on insulinoma cells [1].
• Galanin and its newly discovered relative galanin-like peptide (GALP) are neuropeptides that are implicated in the neuroendocrine regulation of body weight and reproduction [4].

Psychiatry related information on GAL

• We conclude that the distribution of GAL-LI in the sphincter of Oddi and the effect that a pharmacologic dose of GAL has on sphincter of Oddi motor activity, suggests that GAL may be involved in the physiologic control of bile flow in the pig [5].

High impact information on GAL

• BACKGROUND/AIMS: Galanin induces a contraction or a relaxation of digestive smooth muscle [6].
• CONCLUSIONS: Galanin antagonists M15 and M35 inhibit the contraction and the relaxation induced by galanin with different potency, suggesting the presence of distinct galanin receptors in gastrointestinal tract that each mediates a specific effect [6].
• The aim of the study was to evaluate properties of two specific galanin antagonists M15 and M35 on galanin effects on muscle cells [6].
• A galanin receptor protein was solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) from pig brain membranes and then purified by single-step affinity chromatography [7].
• The presence of the 29-amino acid peptide galanin and galanin-like immunoreactivity in the peripheral and central nervous system have been established [8].

Biological context of GAL

• We describe below the construction of a 1.1-million-recombinant cDNA library derived from poly(A)+ RNA from pig adrenal medulla, rich in galanin-like immunoreactivity, and the isolation and characterization of clones encoding preprogalanin [8].
• Sequencing of two recombinant plasmids shows that pig galanin mRNA in the adrenal medulla encodes a precursor protein of 123 amino acids that is comprised of a leader sequence, a single galanin sequence, and a 59-amino acid sequence (galanin message-associated peptide) of as yet unknown function [8].
• Construction of a porcine adrenal medullary cDNA library and nucleotide sequence analysis of two clones encoding a galanin precursor [8].
• Scatchard analysis of binding data reveal one binding process, assuming one binding site per Rh-GAL (n = 1) [1].
• This study on anaesthetised cats compares the effects on cardiac vagal action and blood pressure of human, rat and porcine GAL [9].

Anatomical context of GAL

• Because both of the diffusion times (22 and 700 ms) are much longer as compared to that of unbound Rh-GAL, they correspond to slow-diffusing complexes when Rh-GAL is bound to the cell membranes [1].
• These results suggest that GAL modulates neuronal activity linked to secretomotor function in the porcine small intestine [10].
• Using the indirect immunofluorescence method, the distribution of galanin (GAL)- and galanin message-associated peptide (GMAP)-like immunoreactivities (LI) were studied in sympathetic ganglia and the adrenal gland of the guinea pig [2].
• The role of GAL in prevertebral ganglia is unclear [2].
• In denervation experiments it was revealed that most of the GAL fibers reach the IMG via the lumbar splanchnic nerves [2].

Associations of GAL with chemical compounds

• The single galanin sequence, followed by a glycine (the amide donor), is flanked on both sides by pairs of lysine and arginine residues [8].
• GAL-IR appears to be colocalized with substance P (SP) in fibers of the IMG, indicating an origin of the GAL-containing fibers in dorsal root ganglia (DRG) [2].
• This conclusion was supported by the finding in lumbar DRGs of GAL-positive cell bodies that contained SP [2].
• GAL-induced contractions (GAL EC50 = 9 nmol/l) were maximally 25% of those elicited by 10 mumol/l carbamylcholine and remained unaffected by atropine, tetrodotoxin, or tachyphylaxis to substance P [10].
• The alpha-adrenoceptor blocker phentolamine or the opiate antagonist naloxone did not alter tissue Isc responses to GAL [10].

Physical interactions of GAL

• A small proportion of progesterone receptor-containing perikarya in the medial preoptic area and the mediobasal hypothalamus were bound to be immunoreactive for galanin [11].

Co-localisations of GAL

• DRG BG-projecting neurons contained mostly substance P (SP) and/or calcitonin gene-related peptide (CGRP) which sometimes colocalized with GAL [12].

Regulatory relationships of GAL

• Extirpation of the uterus reduced the expression of TH and induced the expression of GAL in the neurons [13].
• 4. Vasoactive intestinal polypeptide (VIP) and isoprenaline, known to induce cell relaxation through an increase in intracellular cAMP level, inhibited CCK-induced cell contraction at concentrations ranging from 1 pM to 1 microM but failed to inhibit cell contraction induced by galanin [14].
• Galanin inhibits somatostatin release by the rat islet cell tumor in culture, Rin-m [15].
• In conclusion the present study provides some evidence to ascribe a hypophysiotropic role to galanin in regulating LH but not GH secretion in the pig [16].

Other interactions of GAL

• Pancreastatin was effective at all concentrations, but low concentration had more marked secretory effects whereas GAL failed to evoke any significant increases in either protein or amylase secretion [17].
• Carotid-body-like paraganglia from the newborn pig showed cell bodies IR to TH, GAL and ENK [18].
• Immunohistochemistry revealed that FB-positive (FB+) uterus-projecting neurons in control animals contained only immunoreactivities to NPY (ca. 50%) and GAL (single neurons) [19].
• On the contrary, 10 microM forskolin abolished the contraction induced by 10 nM CCK but had no effect on galanin-induced contraction [14].
• Pretreatment of Rin-m cells with pertussis toxin abolished the inhibitory effect of galanin on somatostatin release [15].

Analytical, diagnostic and therapeutic context of GAL

• In the present study an antiserum towards porcine GAL has been developed and used for radioimmunoassay and immunohistochemical studies [20].
• The enteric neuropeptide galanin (GAL) increased the amplitude of spontaneous contractions in longitudinally oriented muscle strips and inhibited short-circuit current (Isc) elevations induced by transmural electrical stimulation (ES) of mucosal sheets from porcine jejunum in vitro [10].
• Hyperacute rejection of hDAF-transgenic pig organ xenografts in cynomolgus monkeys: influence of pre-existing anti-pig antibodies and prevention by the alpha GAL glycoconjugate GAS914 [21].
• Lacrimal gland segments obtained from the abattoir were fixed in paraformaldehyde-picric acid solution, cut into 40-50 microns thick sections and processed for immunohistochemistry using polyclonal antisera against GAL and LEU-ENK [22].
• Infusion of 5.10(-10)-10(-8) M of GAL into the arterial line of the isolated perfused porcine ileum decreased the frequency of spontaneous phasic contractions in a dose-dependent manner [23].

References