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Article: Drug transporters and blood-testis barrier function

TitleDrug transporters and blood-testis barrier function
Authors
Issue Date2011
PublisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.org
Citation
Journal Of Endocrinology, 2011, v. 209 n. 3, p. 337-351 How to Cite?
AbstractThe blood-testis barrier (BTB) creates an immunological barrier that segregates the seminiferous epithelium into the basal and apical compartment. Thus, meiosis I/II and postmeiotic germ cell development take place in a specialized microenvironment in the apical compartment behind the BTB and these events are being shielded from the host immune system. If unwanted drugs and/or chemicals enter the apical compartment from the microvessels in the interstitium via the basal compartment, efflux pumps (e.g. P-glycoprotein) located in Sertoli cells and/or spermatids can actively transport these molecules out of the apical compartment. However, the mechanism(s) by which influx pumps regulate the entry of drugs/chemicals into the apical compartment is not known. In this study, a solute carrier (SLC) transporter organic anion transporting polypeptide 3 (Oatp3, Slco1a5) was shown to be an integrated component of the N-cadherin-based adhesion complex at the BTB. However, a knockdown of Oatp3 alone or in combination with three other major Sertoli cell drug influx pumps, namely Slc22a5, Slco6b1, and Slco6c1, by RNAi using corresponding specific siRNA duplexes failed to perturb the Sertoli cell tight junction (TJ) permeability barrier function. Yet, the transport of [3H]adjudin, a potential male contraceptive that is considered a toxicant to spermatogenesis, across the BTB was impeded following the knockdown of either Oatp3 or all the four SLC transporters. In short, even though drug transporters (e.g. influx pumps) are integrated components of the adhesion protein complexes at the BTB, they are not involved in regulating the Sertoli cell TJ permeability barrier function, instead they are only involved in the transport of drugs, such as adjudin, across the immunological barrier at the BTB. © 2011 Society for Endocrinology.
Persistent Identifierhttp://hdl.handle.net/10722/140889
ISSN
2015 Impact Factor: 4.498
2015 SCImago Journal Rankings: 1.910
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of HealthNICHD
R01 HD056034
R01 HD056034-02-S1
U54 HD029990
R03 HD 061401
University of Hong Kong
Funding Information:

This research was supported by grants from the National Institutes of Health (NICHD, R01 HD056034 and R01 HD056034-02-S1 to C Y C; U54 HD029990 Project 5 to C Y C; R03 HD 061401 to DDM); and Research Grant Councils and Committee for Research and Conference Grants (CRGG) of the University of Hong Kong to WML.

References

 

DC FieldValueLanguage
dc.contributor.authorSu, Len_HK
dc.contributor.authorMruk, DDen_HK
dc.contributor.authorLee, WMen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2011-09-23T06:20:59Z-
dc.date.available2011-09-23T06:20:59Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Endocrinology, 2011, v. 209 n. 3, p. 337-351en_HK
dc.identifier.issn0022-0795en_HK
dc.identifier.urihttp://hdl.handle.net/10722/140889-
dc.description.abstractThe blood-testis barrier (BTB) creates an immunological barrier that segregates the seminiferous epithelium into the basal and apical compartment. Thus, meiosis I/II and postmeiotic germ cell development take place in a specialized microenvironment in the apical compartment behind the BTB and these events are being shielded from the host immune system. If unwanted drugs and/or chemicals enter the apical compartment from the microvessels in the interstitium via the basal compartment, efflux pumps (e.g. P-glycoprotein) located in Sertoli cells and/or spermatids can actively transport these molecules out of the apical compartment. However, the mechanism(s) by which influx pumps regulate the entry of drugs/chemicals into the apical compartment is not known. In this study, a solute carrier (SLC) transporter organic anion transporting polypeptide 3 (Oatp3, Slco1a5) was shown to be an integrated component of the N-cadherin-based adhesion complex at the BTB. However, a knockdown of Oatp3 alone or in combination with three other major Sertoli cell drug influx pumps, namely Slc22a5, Slco6b1, and Slco6c1, by RNAi using corresponding specific siRNA duplexes failed to perturb the Sertoli cell tight junction (TJ) permeability barrier function. Yet, the transport of [3H]adjudin, a potential male contraceptive that is considered a toxicant to spermatogenesis, across the BTB was impeded following the knockdown of either Oatp3 or all the four SLC transporters. In short, even though drug transporters (e.g. influx pumps) are integrated components of the adhesion protein complexes at the BTB, they are not involved in regulating the Sertoli cell TJ permeability barrier function, instead they are only involved in the transport of drugs, such as adjudin, across the immunological barrier at the BTB. © 2011 Society for Endocrinology.en_HK
dc.languageengen_US
dc.publisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.orgen_HK
dc.relation.ispartofJournal of Endocrinologyen_HK
dc.subject.meshBiological Transport-
dc.subject.meshBlood-Testis Barrier - metabolism-
dc.subject.meshCadherins - metabolism-
dc.subject.meshOrganic Anion Transporters, Sodium-Independent - metabolism-
dc.subject.meshSertoli Cells - cytology - metabolism-
dc.titleDrug transporters and blood-testis barrier functionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-0795&volume=209&issue=3&spage=337&epage=351&date=2011&atitle=Drug+transporters+and+blood-testis+barrier+function-
dc.identifier.emailLee, WM: hrszlwm@hku.hken_HK
dc.identifier.authorityLee, WM=rp00728en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1530/JOE-10-0474en_HK
dc.identifier.pmid21471187-
dc.identifier.scopuseid_2-s2.0-79958187254en_HK
dc.identifier.hkuros194356en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79958187254&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume209en_HK
dc.identifier.issue3en_HK
dc.identifier.spage337en_HK
dc.identifier.epage351en_HK
dc.identifier.isiWOS:000291981300010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridSu, L=34871019700en_HK
dc.identifier.scopusauthoridMruk, DD=6701823934en_HK
dc.identifier.scopusauthoridLee, WM=24799156600en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK

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