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Article: Studies of the renal action of melatonin: evidence that the effects are mediated by 37 kDa receptors of the Mel1a subtype localized primarily to the basolateral membrane of the proximal tubule

TitleStudies of the renal action of melatonin: evidence that the effects are mediated by 37 kDa receptors of the Mel1a subtype localized primarily to the basolateral membrane of the proximal tubule
Authors
Issue Date1997
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
Faseb Journal, 1997, v. 11 n. 1, p. 93-100 How to Cite?
AbstractThe pineal hormone melatonin controls circadian behavior of a variety of organs in different species, including humans. However, the precise mechanism (or mechanisms) by which this occurs remains largely unknown. At the cellular level its effects are believed to be mediated via interaction with specific melatonin receptors (MR), which have previously been cloned from human brain (Mel(1a)) and retina (Mel(1b)). At the tissue level, MR have been investigated primarily through empirical definition of specific binding sites, but so far there has been little success in biochemical or molecular characterization of native MR. In the kidney, there is strong circumstantial evidence that melatonin affects diurnal variations in renal function, but relatively little is known about the overall glomerular vs. tubular contributions to these effects. The strategy behind the present study was to use a panel of peptide-specific antibodies to identify MR proteins in various tissues, and from a determination of the intrarenal distribution of MR, gain insight into the mechanism by which melatonin might regulate kidney function. We used two peptide-specific antibodies directed against different regions of Mel(1a) to identify MR. Our results show that the native Mel(1a) receptor is a 37 kilodalton (kDa) protein in human and rat brain. Further, immunofluorescent studies carried out in guinea pig kidney have revealed that anti-Mel(1a) antibody is also localized to the basolateral membrane (BLM) of the renal cortical epithelium, especially the early proximal tubule. Immunoblotting of purified BLM fractions from guinea pig renal cortex and small intestine using the two different peptide-specific antibodies reveals the presence of a single peptide-blockable band at 37 kDa. These same BLM fractions also demonstrate the presence of high-affinity 2- [125I]iodomelatonin (125I-MEL) binding sites, with the pharmacological specificity of binding expected of the Mel(1a) receptor subtype, inhibited by guanosine 5'-O-(3-thiotriphosphate) (GTPγS) and pertussis toxin. We conclude that functional MR in guinea pig kidney and small intestine are of the Mel(1a) subtype, and are expressed as 37 kDa proteins localized to the BLM and coupled to a pertussis toxin-sensitive G-protein (Gi). This localization strongly suggests that the proximal tubule plays a significant role in mediating the renal action of melatonin.
Persistent Identifierhttp://hdl.handle.net/10722/149564
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSong, Yen_US
dc.contributor.authorChan, CWYen_US
dc.contributor.authorBrown, GMen_US
dc.contributor.authorPang, SFen_US
dc.contributor.authorSilverman, Men_US
dc.date.accessioned2012-06-26T05:55:20Z-
dc.date.available2012-06-26T05:55:20Z-
dc.date.issued1997en_US
dc.identifier.citationFaseb Journal, 1997, v. 11 n. 1, p. 93-100en_US
dc.identifier.issn0892-6638en_US
dc.identifier.urihttp://hdl.handle.net/10722/149564-
dc.description.abstractThe pineal hormone melatonin controls circadian behavior of a variety of organs in different species, including humans. However, the precise mechanism (or mechanisms) by which this occurs remains largely unknown. At the cellular level its effects are believed to be mediated via interaction with specific melatonin receptors (MR), which have previously been cloned from human brain (Mel(1a)) and retina (Mel(1b)). At the tissue level, MR have been investigated primarily through empirical definition of specific binding sites, but so far there has been little success in biochemical or molecular characterization of native MR. In the kidney, there is strong circumstantial evidence that melatonin affects diurnal variations in renal function, but relatively little is known about the overall glomerular vs. tubular contributions to these effects. The strategy behind the present study was to use a panel of peptide-specific antibodies to identify MR proteins in various tissues, and from a determination of the intrarenal distribution of MR, gain insight into the mechanism by which melatonin might regulate kidney function. We used two peptide-specific antibodies directed against different regions of Mel(1a) to identify MR. Our results show that the native Mel(1a) receptor is a 37 kilodalton (kDa) protein in human and rat brain. Further, immunofluorescent studies carried out in guinea pig kidney have revealed that anti-Mel(1a) antibody is also localized to the basolateral membrane (BLM) of the renal cortical epithelium, especially the early proximal tubule. Immunoblotting of purified BLM fractions from guinea pig renal cortex and small intestine using the two different peptide-specific antibodies reveals the presence of a single peptide-blockable band at 37 kDa. These same BLM fractions also demonstrate the presence of high-affinity 2- [125I]iodomelatonin (125I-MEL) binding sites, with the pharmacological specificity of binding expected of the Mel(1a) receptor subtype, inhibited by guanosine 5'-O-(3-thiotriphosphate) (GTPγS) and pertussis toxin. We conclude that functional MR in guinea pig kidney and small intestine are of the Mel(1a) subtype, and are expressed as 37 kDa proteins localized to the BLM and coupled to a pertussis toxin-sensitive G-protein (Gi). This localization strongly suggests that the proximal tubule plays a significant role in mediating the renal action of melatonin.en_US
dc.languageengen_US
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/en_US
dc.relation.ispartofFASEB Journalen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBasement Membrane - Metabolismen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshBrain - Metabolismen_US
dc.subject.meshElectrophoresis, Polyacrylamide Gelen_US
dc.subject.meshEpithelium - Metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshFluorescent Antibody Technique, Indirecten_US
dc.subject.meshGuinea Pigsen_US
dc.subject.meshHumansen_US
dc.subject.meshIntestine, Small - Metabolismen_US
dc.subject.meshKidney Cortex - Metabolismen_US
dc.subject.meshKidney Tubules, Proximal - Metabolismen_US
dc.subject.meshMaleen_US
dc.subject.meshMelatonin - Analogs & Derivatives - Metabolismen_US
dc.subject.meshMolecular Weighten_US
dc.subject.meshRabbitsen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReceptors, Cell Surface - Chemistry - Metabolismen_US
dc.subject.meshReceptors, Cytoplasmic And Nuclear - Chemistry - Metabolismen_US
dc.subject.meshReceptors, Melatoninen_US
dc.titleStudies of the renal action of melatonin: evidence that the effects are mediated by 37 kDa receptors of the Mel1a subtype localized primarily to the basolateral membrane of the proximal tubuleen_US
dc.typeArticleen_US
dc.identifier.emailChan, CWY:camchan@hku.hken_US
dc.identifier.authorityChan, CWY=rp01311en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.pmid9034171-
dc.identifier.scopuseid_2-s2.0-0031038880en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0031038880&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume11en_US
dc.identifier.issue1en_US
dc.identifier.spage93en_US
dc.identifier.epage100en_US
dc.identifier.isiWOS:A1997WK14700013-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridSong, Y=7404920869en_US
dc.identifier.scopusauthoridChan, CWY=12240386600en_US
dc.identifier.scopusauthoridBrown, GM=35493704500en_US
dc.identifier.scopusauthoridPang, SF=7402528719en_US
dc.identifier.scopusauthoridSilverman, M=7403299191en_US
dc.customcontrol.immutablecsl 130319-

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