Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-5-26
pubmed:abstractText
Cubilin and megalin are multifunctional endocytotic receptors expressed in many absorptive epithelia. The receptors have separate functions but may act in concert in several tissues including the small intestine, the visceral yolk sac and the renal proximal tubule to perform significant physiological functions essential to homeostasis in the extracellular fluid compartments. Because of the importance of fluid homeostasis in the inner ear, we investigated the expression of cubilin and megalin in this structure. Furthermore, we examined the binding properties of 6 different aminoglycosides (AGs) to cubilin and compared the results to data obtained for megalin, which is a well-known receptor for AGs and other polybasic substances, including several ototoxic drugs. In the cochlea, immunohistochemical labelling for cubilin showed expression corresponding to the apical surface of the strial marginal cells, to epithelial cells at the spiral prominence and to epithelial cells of Reissner's membrane facing the cochlear duct. In the vestibular apparatus, positive labelling was found in dark cells of the utricle and those flanking the crista ampullaris of the semicircular canals. Exactly the same tissue distribution was found for megalin. These findings support the prevailing view that cubilin and megalin constitute a dual-receptor complex facilitating the function of each other. The physiological role of this receptor complex in the inner ear remains unknown, although several established ligands for both cubilin and megalin are present in the inner ear fluids. Receptor-ligand interaction analysis showed that all 6 AGs bind to both receptors and with approximately the same affinity. The results demonstrate a novel role for cubilin as a drug receptor for AGs and possibly other ototoxic substances.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1421-9700
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
267-78
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Cubilin and megalin co-localize in the neonatal inner ear.
pubmed:affiliation
Department of Otorhinolaryngology, Aarhus University Hospital, Aarhus, Denmark. tauris@dadlnet.dk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't