title: A putative nicotine pump at the metabolic blood-brain barrier of the tobacco hornworm.
abstract: In mammals, P-glycoprotein immunostaining at the blood-brain barrier has implicated the multidrug pump in the restricted movement of many cytotoxic agents into the central nervous system (CNS). Since many insects require a sophisticated blood-brain barrier system to protect their CNS from plant-derived neurotoxins, we have investigated the possibility that a P-glycoprotein homolog constitutes a component of the insect blood-brain barrier. We have used the nicotine-resistant tobacco hornworm (Manduca sexta) to address this issue. Manduca has been previously shown, in physiological studies, to have an alkaloid (nicotine/morphine/atropine) pump at its excretory malpighian tubules. We show (1) that the tubules are P-glycoprotein immunopositive, (2) that Manduca has a metabolic blood-brain barrier for nicotine, (3) that the barrier co-localizes with P-glycoprotein immunostaining, and (4) that detoxifying enzymes as well as the nicotine pump are likely to account for the metabolic blood-brain barrier to nicotine. These findings may provide insights on two major fronts, the troublesome problem of multi-insecticide resistance, a phenomenon that parallels multidrug resistance in tumor cells, and the problem of tolerance to addictive neuroactive drugs like nicotine or morphine.
authors.affiliation: Department of Biology, University of Ottawa (K1N 6N5), Ontario, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Murray
authors.forename: M
authors.initials: M
authors.lastname: Quaglia
authors.forename: J T
authors.initials: JT
authors.lastname: Arnason
authors.forename: C E
authors.initials: CE
authors.lastname: Morris
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D001345:Autoradiography; D001812:Blood-Brain Barrier / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D002855:Chromatography, Thin Layer; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D016623:Ion Pumps; D008317:Malpighian Tubules / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D009036:Moths / Q000378:metabolism*; D009538:Nicotine / Q000378:metabolism*; D010526:Periplaneta; D010882:Piperonyl Butoxide / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D016623:Ion Pumps; D008562:Membrane Glycoproteins; D009538:Nicotine; D002217:Carbachol; D010882:Piperonyl Butoxide