title: Cloning and characterization of glutamate receptors in Californian sea lions (Zalophus californianus).
abstract: Domoic acid produced by marine algae has been shown to cause acute and chronic neurologic sequelae in Californian sea lions following acute or low-dose exposure. Histological findings in affected animals included a degenerative cardiomyopathy that was hypothesized to be caused by over-excitation of the glutamate receptors (GluRs) speculated to be present in the sea lion heart. Thus tissues from five sea lions without lesions associated with domoic acid toxicity and one animal with domoic acid-induced chronic neurologic sequelae and degenerative cardiomyopathy were examined for the presence of GluRs. Immunohistochemistry localized mGluR 2/3, mGluR 5, GluR 2/3 and NMDAR 1 in structures of the conducting system and blood vessels. NMDAR 1 and GluR 2/3 were the most widespread as immunoreactivity was observed within sea lion conducting system structures. PCR analysis, cloning and subsequent sequencing of the seal lion GluRs showed only 80% homology to those from rats, but more than 95% homologous to those from dogs. The cellular distribution and expression of subtypes of GluRs in the sea lion hearts suggests that exposure to domoic acid may induce cardiac damage and functional disturbances.
authors.affiliation: Health Canada, Toxicology Research Division, Banting Bldg, Tunney's Pasture, Ottawa, Ontario, K1A 0L2, Canada. Santokh_Gill@hc-sc.gc.ca
authors.forename: Santokh
authors.initials: S
authors.lastname: Gill
authors.forename: Tracey
authors.initials: T
authors.lastname: Goldstein
authors.forename: Donna
authors.initials: D
authors.lastname: Situ
authors.forename: Tanja S
authors.initials: TS
authors.lastname: Zabka
authors.forename: Frances M D
authors.initials: FM
authors.lastname: Gulland
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Mueller
mesh_terms: D000818:Animals; D001483:Base Sequence; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism / Q000662:veterinary*; D003001:Cloning, Molecular; D017931:DNA Primers; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D008387:Marine Toxins / Q000633:toxicity*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry*; D009498:Neurotoxins / Q000633:toxicity; D016133:Polymerase Chain Reaction; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification*; D046070:Sea Lions / Q000502:physiology*
chemical_list: D017931:DNA Primers; D008387:Marine Toxins; D009498:Neurotoxins; D017470:Receptors, Glutamate; C012301:domoic acid; D007608:Kainic Acid