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Article: Modulation of blood glucose by melatonin: A direct action on melatonin receptors in mouse hepatocytes

TitleModulation of blood glucose by melatonin: A direct action on melatonin receptors in mouse hepatocytes
Authors
Issue Date2001
PublisherS Karger AG. The Journal's web site is located at http://www.karger.com/NSG
Citation
Biological Signals And Receptors, 2001, v. 10 n. 6, p. 367-379 How to Cite?
AbstractMelatonin receptors were studied in isolated mouse hepatocytes using the 2[125I]iodomelatonin binding assay. The binding of 2[125I]iodomelatonin to hepatocytes isolated from the mouse using collagenase was stable, saturable, reversible and of high affinity. The equilibrium dissociation constant (Kd) obtained from saturation studies was 10.0 ± 0.4 pmol/l (n = 16), which was comparable to the Kd obtained from kinetics studies (6.9 ± 1.2 pmol/l, n = 3), and the maximum number of binding sites (Bmax) was 2.9 ± 0.4 fmol/mg protein (n = 16). The relative order of potency of indoles in competing for 2[125I]iodomelatonin binding was 2-iodomelatonin > 2-phenylmelatonin > 6-chloromelatonin > melatonin > 6-hydroxymelatonin > N-acetylserotonin, indicating that the binding was mediated by the ML1 receptor subtype. The linear Rosenthal plots, the close proximity of the Hill coefficient to unity and the monophasic competition curves suggest that a single class of 2[125I]iodomelatonin binding sites is present in the mouse hepatocytes. Guanosine 5′-O-(3-thiotriphosphate) dose-dependently inhibited 2[125I]iodomelatonin by lowering the affinity of binding, while no inhibitory effects of adenosine nucleotides were observed, suggesting that the binding sites are G-protein linked. Western immunoblotting was used to identify the melatonin receptor subtype in mouse hepatocytes using anti-Mel1a and anti-Mel1b. Hepatocyte membrane extract reacted with anti-Mel1b but not anti-Mel1a giving a peptide-blockable band of 36 kD, supporting the hypothesis that the melatonin receptors in mouse hepatocytes are of the Mel1b subtype. Melatonin injection and a high plasma glucose level affected 2[125I]iodomelatonin binding in the whole mouse liver homogenates. Plasma glucose was elevated by mid-light intraperitoneal injection of melatonin (4 and 40 mg/kg body weight) in a dose-dependent manner with maximum elevation achieved 1 h after injection. 2[125I]Iodomelatonin binding at this time showed increased Kd with no changes in Bmax. When the plasma glucose returned to normal within 2 h, the binding remained lowered with increased Kd but no changes in Bmax. Elevation of plasma glucose by 2-deoxyglucose injection (500 mg/kg), on the other hand, decreased the binding by decreasing the Bmax without affecting the Kd. Suppression of plasma glucose by insulin injection (3 IU/kg) did not change the binding. Thus, melatonin may act directly on the liver to elevate the plasma glucose level, and changes in plasma glucose level itself may in turn affect hepatic melatonin binding. Copyright © 2001 S. Karger AG, Basel.
Persistent Identifierhttp://hdl.handle.net/10722/171696
ISSN
2003 Impact Factor: 3.5
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPoon, AMSen_US
dc.contributor.authorChoy, EHYen_US
dc.contributor.authorPang, SFen_US
dc.date.accessioned2012-10-30T06:16:25Z-
dc.date.available2012-10-30T06:16:25Z-
dc.date.issued2001en_US
dc.identifier.citationBiological Signals And Receptors, 2001, v. 10 n. 6, p. 367-379en_US
dc.identifier.issn1422-4933en_US
dc.identifier.urihttp://hdl.handle.net/10722/171696-
dc.description.abstractMelatonin receptors were studied in isolated mouse hepatocytes using the 2[125I]iodomelatonin binding assay. The binding of 2[125I]iodomelatonin to hepatocytes isolated from the mouse using collagenase was stable, saturable, reversible and of high affinity. The equilibrium dissociation constant (Kd) obtained from saturation studies was 10.0 ± 0.4 pmol/l (n = 16), which was comparable to the Kd obtained from kinetics studies (6.9 ± 1.2 pmol/l, n = 3), and the maximum number of binding sites (Bmax) was 2.9 ± 0.4 fmol/mg protein (n = 16). The relative order of potency of indoles in competing for 2[125I]iodomelatonin binding was 2-iodomelatonin > 2-phenylmelatonin > 6-chloromelatonin > melatonin > 6-hydroxymelatonin > N-acetylserotonin, indicating that the binding was mediated by the ML1 receptor subtype. The linear Rosenthal plots, the close proximity of the Hill coefficient to unity and the monophasic competition curves suggest that a single class of 2[125I]iodomelatonin binding sites is present in the mouse hepatocytes. Guanosine 5′-O-(3-thiotriphosphate) dose-dependently inhibited 2[125I]iodomelatonin by lowering the affinity of binding, while no inhibitory effects of adenosine nucleotides were observed, suggesting that the binding sites are G-protein linked. Western immunoblotting was used to identify the melatonin receptor subtype in mouse hepatocytes using anti-Mel1a and anti-Mel1b. Hepatocyte membrane extract reacted with anti-Mel1b but not anti-Mel1a giving a peptide-blockable band of 36 kD, supporting the hypothesis that the melatonin receptors in mouse hepatocytes are of the Mel1b subtype. Melatonin injection and a high plasma glucose level affected 2[125I]iodomelatonin binding in the whole mouse liver homogenates. Plasma glucose was elevated by mid-light intraperitoneal injection of melatonin (4 and 40 mg/kg body weight) in a dose-dependent manner with maximum elevation achieved 1 h after injection. 2[125I]Iodomelatonin binding at this time showed increased Kd with no changes in Bmax. When the plasma glucose returned to normal within 2 h, the binding remained lowered with increased Kd but no changes in Bmax. Elevation of plasma glucose by 2-deoxyglucose injection (500 mg/kg), on the other hand, decreased the binding by decreasing the Bmax without affecting the Kd. Suppression of plasma glucose by insulin injection (3 IU/kg) did not change the binding. Thus, melatonin may act directly on the liver to elevate the plasma glucose level, and changes in plasma glucose level itself may in turn affect hepatic melatonin binding. Copyright © 2001 S. Karger AG, Basel.en_US
dc.languageengen_US
dc.publisherS Karger AG. The Journal's web site is located at http://www.karger.com/NSGen_US
dc.relation.ispartofBiological Signals and Receptorsen_US
dc.subject.meshAdenine Nucleotides - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBinding, Competitiveen_US
dc.subject.meshBlood Glucose - Metabolismen_US
dc.subject.meshDeoxyglucose - Pharmacologyen_US
dc.subject.meshGuanine Nucleotides - Pharmacologyen_US
dc.subject.meshHepatocytes - Drug Effects - Metabolismen_US
dc.subject.meshHyperglycemia - Metabolismen_US
dc.subject.meshHypoglycemia - Metabolismen_US
dc.subject.meshInsulin - Pharmacologyen_US
dc.subject.meshKineticsen_US
dc.subject.meshMelatonin - Analogs & Derivatives - Metabolism - Pharmacologyen_US
dc.subject.meshMiceen_US
dc.subject.meshReceptors, Cell Surface - Classification - Drug Effects - Metabolismen_US
dc.subject.meshReceptors, Cytoplasmic And Nuclear - Classification - Drug Effects - Metabolismen_US
dc.subject.meshReceptors, Melatoninen_US
dc.titleModulation of blood glucose by melatonin: A direct action on melatonin receptors in mouse hepatocytesen_US
dc.typeArticleen_US
dc.identifier.emailPoon, AMS:amspoon@hkucc.hku.hken_US
dc.identifier.authorityPoon, AMS=rp00354en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid11721092-
dc.identifier.scopuseid_2-s2.0-0035200294en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035200294&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume10en_US
dc.identifier.issue6en_US
dc.identifier.spage367en_US
dc.identifier.epage379en_US
dc.identifier.isiWOS:000172784600003-
dc.publisher.placeSwitzerlanden_US
dc.identifier.scopusauthoridPoon, AMS=7103068868en_US
dc.identifier.scopusauthoridChoy, EHY=7005149649en_US
dc.identifier.scopusauthoridPang, SF=7402528719en_US

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