Disease relevance of GAL

• Galanin inhibits insulin secretion and induces hyperglycemia in dogs [1].
• The contraction induced by galanin was abolished; the CCK-induced contraction was unchanged by pertussis toxin [2].
• The effects of galanin on gastric acid secretion and plasma levels of gastrin were studied in conscious dogs chronically fitted with gastric fistulas [3].
• Corelease of galanin and NE from pancreatic sympathetic nerves during severe hypoglycemia in dogs [4].
• Substance P-, vasoactive intestinal polypeptide-, galanin-, and neuropeptide Y-immunoreactive neurons were found in this ganglion, and the vasoactive intestinal polypeptide-immunoreactive neurons were the most abundant [5].

Psychiatry related information on GAL

• During stimulated contractions, galanin inhibited phasic motor activity within 2 minutes of initiation of the infusion; this inhibition may result from direct smooth previously reported muscle inhibition [6].

High impact information on GAL

• Galanin inhibition of vasoactive intestinal polypeptide release and circular muscle motility in the isolated perfused canine ileum [6].
• Galanin infusions (9-minute) inhibited vasoactive intestinal polypeptide release in a concentration-dependent manner (maximum during minutes 8-10) irrespective of the absence (quiescence) or presence of phasic circular muscle contractions induced by local electrical field stimulation of nerves [6].
• Galanin infusions produced greater parenteral glucose-induced rises in plasma glucose levels along with markedly blunted insulin responses compared with glucose and insulin responses to control glucose infusions [1].
• Intravenous administration of galanin into fasted conscious dogs produced a dose-dependent hyperglycemia accompanied by decreases in plasma insulin levels, but with no elevation of plasma glucagon levels [1].
• Immediately after cessation of the galanin infusions, elevation of plasma insulin levels occurred in the basal state and after parenteral glucose loading [1].

Chemical compound and disease context of GAL

• We conclude that NE and galanin are coreleased from pancreatic sympathetic nerves when these nerves are centrally activated during severe hypoglycemia in halothane-anesthetized dogs [4].
• To determine whether norepinephrine (NE) and galanin are coreleased during reflex activation of the sympathetic nervous system by hypoglycemia, we administered insulin to halothane-anesthetized (0.8%) dogs and measured the spillover of NE and galanin-like immunoreactivity (GLIR) into pancreatic venous plasma [4].
• Kinetic and competition studies using guanosine 5'-O-(3-thiotriphosphate) or pertussis toxin (PTX) suggested that the high-affinity binding site involved a PTX-sensitive G protein which acted to slow dissociation of bound galanin from the receptor [7].

Biological context of GAL

• The predicted amino acid sequence differs from the other known species of galanin by three to six amino acids in the C-terminal half of the molecule [8].
• It is likely that endogenous hepatic galanin acts directly on the liver to selectively modulate norepinephrine's metabolic action, whereas endogenous hepatic NPY acts independently of NE to cause vasoconstriction [9].
• Although recent data point to a possible indirect role for galanin in modulating renal blood flow (RBF) and fluid homeostasis in experimental animals, there have been no systematic studies exploring the possible direct effects of the peptide on the mammalian kidney [10].
• We ascertained the RBF, glomerular filtration rate (GFR) and plasma glucose responses to direct intrarenal infusion of three progressively increasing doses of synthetic galanin in anesthetized dogs [10].

Anatomical context of GAL

• These data support the hypothesis that galanin is a sympathetic neurotransmitter in dog pancreas [8].
• To determine if dog galanin is a potent inhibitor of dog insulin secretion we determined its primary structure from its cloned cDNA, evaluated its expression in celiac ganglia and determined its effect on islet hormone secretion [8].
• Immunohistochemical analysis of dog stellate ganglia and cardiac muscle showed that most nerve cell bodies showing tyrosine hydroxylase immunoreactivity (TH-IR) also showed immunoreactivity to both NPY and GAL [11].
• Numerous nerve cell bodies with VIP and GAL immunoreactivity and a few with SP ENK, and NPY immunoreactivity were observed [12].
• Our previous studies have demonstrated the presence of a considerable number of substance P-, calcitonin gene-related peptide (CGRP)-, and galanin-like immunoreactive (LI) nerve fibers in the anterior pituitary in several mammalian species [13].

Associations of GAL with chemical compounds

• These results suggest that in the conscious dog, galanin administration produces a relatively selective, but readily reversible, inhibition of insulin secretion stimulated by oral nutrients or iv arginine [14].
• Similarly, tolbutamide administration during saline infusions elevated plasma insulin levels to a peak value of 28.6 +/- 6.2 microU/ml but during galanin infusions, the peak value seen after tolbutamide administration was 4.8 +/- 1.6 microU/ml [15].
• Finally, NPY, but not galanin, tended to decrease HAC when infused alone; neither neuropeptide potentiated the HAC response to NE [9].
• Incubation of cells in Ca(2+)-free medium or in the presence of nifedipine caused an inhibition of galanin-induced contraction whereas it had no effect on the contraction induced by CCK8 [2].
• Galanin (2-4 micrograms.kg-1 i.v.) also depressed the secretory response to 2-deoxy-D-glucose without significantly affecting plasma gastrin levels [3].

Co-localisations of GAL

• Galanin was also found in hepatic nerves usually co-localized with tyrosine hydroxylase, a sympathetic marker [16].

Regulatory relationships of GAL

• Somatostatin secretion was inhibited by galanin (p less than 0.001), but not by any of the other investigated peptides [17].

Other interactions of GAL

• It potently inhibited insulin secretion, less potently inhibited pancreatic somatostatin release and stimulated glucagon secretion, similar to the effects of porcine galanin in the dog [8].
• Preincubation of cells with somatostatin, N-ethylmaleimide, and (R)-p-cAMPS inhibited galanin- and VIP-induced relaxation [2].
• In the celiac ganglion, virtually all cell bodies were positive for both galanin and TH; a large subpopulation of these cells were also positive for NPY [18].
• No immunoreactive neurons were observed with the available antisera to galanin, gastrin-releasing peptide, and motilin [19].

Analytical, diagnostic and therapeutic context of GAL

• Equimolar intravenous injections of galanin (GAL) had no effect on cardiac vagal action in this species [11].
• Intravenous infusion of galanin into conscious dogs during ingestion of oral glucose or a mixed meal or during iv infusion of arginine resulted in significant blunting of plasma insulin responses and significant increases in plasma glucose levels compared to those in control experiments [14].
• Radioimmunoassay (RIA) of galanin in extracts of dog celiac ganglion revealed a very high content (256 +/- 33 pmol/g wet weight) of galanin-like immunoreactivity (GLIR), consistent with the dense staining observed [18].
• The distribution of nerves containing galanin immunoreactivity (GAL-IR) in the canine gastrointestinal tract was determined by immunohistochemistry [20].
• The metabolic response to graded decreases in insulin concentration was evaluated by measuring the concentration, production, and metabolic clearance rate of glucose in response to the infusion of different galanin doses (1-12 micrograms/kg/h) in 18-h fasted dogs [21].

References