干旱区生态环境知识资源中心(Arid): Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model

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DOI	10.1002/prp2.50
	Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model
	Andersson, Olga; Badisco, Liesbeth; Hansen, Ane Hakansson; Hansen, Steen Honore; Hellman, Karin; Nielsen, Peter Aadal; Olsen, Line Rorbaek; Verdonck, Rik; Abbott, N. Joan; Vanden Broeck, Jozef; Andersson, Gunnar
通讯作者	Andersson, G
来源期刊	PHARMACOLOGY RESEARCH & PERSPECTIVES
ISSN	2052-1707
出版年	2014
卷号	2 期号:4
英文摘要	In earlier studies insects were proposed as suitable models for vertebrate bloodbrain barrier (BBB) permeability prediction and useful in early drug discovery. Here we provide transcriptome and functional data demonstrating the presence of a P-glycoprotein (Pgp) efflux transporter in the brain barrier of the desert locust (Schistocerca gregaria). In an in vivo study on the locust, we found an increased uptake of the two well-known Pgp substrates, rhodamine 123 and loperamide after co-administration with the Pgp inhibitors cyclosporine A or verapamil. Furthermore, ex vivo studies on isolated locust brains demonstrated differences in permeation of high and low permeability compounds. The vertebrate Pgp inhibitor verapamil did not affect the uptake of passively diffusing compounds but significantly increased the brain uptake of Pgp substrates in the ex vivo model. In addition, studies at 2 degrees C and 30 degrees C showed differences in brain uptake between Pgp-effluxed and passively diffusing compounds. The transcriptome data show a high degree of sequence identity of the locust Pgp transporter protein sequences to the human Pgp sequence (37%), as well as the presence of conserved domains. As in vertebrates, the locust brain-barrier function is morphologically confined to one specific cell layer and by using a whole-brain ex vivo drug exposure technique our locust model may retain the major cues that maintain and modulate the physiological function of the brain barrier. We show that the locust model has the potential to act as a robust and convenient model for assessing BBB permeability in early drug discovery.
英文关键词	Brain-barrier permeability efflux transporter insect brain barrier Pgp-transporter screening model
类型	Article
语种	英语
开放获取类型	DOAJ Gold, Green Published
收录类别	ESCI
WOS记录号	WOS:000410316000001
WOS关键词	CENTRAL-NERVOUS-SYSTEM ; DRUG DISCOVERY ; BLOOD ; TRANSPORTERS ; ASSAYS ; PREDICT ; CNS
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
来源机构	University of London
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/330852
作者单位	[Andersson, Olga; Hansen, Ane Hakansson; Hellman, Karin; Nielsen, Peter Aadal; Andersson, Gunnar] Entomo Pharm R&D, S-22381 Lund, Sweden; [Badisco, Liesbeth; Verdonck, Rik; Vanden Broeck, Jozef] Katholieke Univ Leuven, Dept Anim Physiol & Neurobiol, Leuven, Belgium; [Hansen, Steen Honore; Olsen, Line Rorbaek] Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-2100 Copenhagen, Denmark; [Abbott, N. Joan] Kings Coll London, Inst Pharmaceut Sci, BBB Grp, London SE1 9NH, England
推荐引用方式 GB/T 7714	Andersson, Olga,Badisco, Liesbeth,Hansen, Ane Hakansson,et al. Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model[J]. University of London,2014,2(4).
APA	Andersson, Olga.,Badisco, Liesbeth.,Hansen, Ane Hakansson.,Hansen, Steen Honore.,Hellman, Karin.,...&Andersson, Gunnar.(2014).Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model.PHARMACOLOGY RESEARCH & PERSPECTIVES,2(4).
MLA	Andersson, Olga,et al."Characterization of a novel brain barrier ex vivo insect-based P-glycoprotein screening model".PHARMACOLOGY RESEARCH & PERSPECTIVES 2.4(2014).