title: The effects of A1 and A2A adenosine receptor agonists on kainic acid excitotoxicity in the guinea pig cochlea.
abstract: The present study aimed to clarify the protective effect of adenosine receptors against the excitotoxicity of cochlear afferent dendrites. The effects of 2-chloro-N6-cyclopentyladenosine (CCPA), an A1 adenosine receptor agonist, and 5'-N-cyclopropyl-carboxamidoadenosine (CPCA), an A2A adenosine receptor agonist, on cochlear excitotoxicity induced by kainic acid (KA) were examined using guinea pigs. KA was applied to the round window membrane at a concentration of 10mM for 30 min. CCPA or CPCA was given at the onset of KA application. KA morphologically induced the swelling of cochlear afferent dendrites and significantly elevated the threshold of the compound action potential (CAP) of the cochlea. CCPA inhibited the KA-induced CAP threshold shift and swelling of the cochlear afferent dendrites. However, CPCA did not affect cochlear excitotoxicity induced by KA. The results suggest that adenosine A1 receptor activation could prevent the excitotoxicity of cochlear afferent dendrites.
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. ktabuchi@md.tsukuba.ac.jp
authors.forename: Keiji
authors.initials: K
authors.lastname: Tabuchi
authors.forename: Shuhei
authors.initials: S
authors.lastname: Sakai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakayama
authors.forename: Bungo
authors.initials: B
authors.lastname: Nishimura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirose
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology*; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D003051:Cochlea / Q000187:drug effects*; D003712:Dendrites / Q000187:drug effects; D006168:Guinea Pigs; D007608:Kainic Acid / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D018696:Neuroprotective Agents; D043682:Receptor, Adenosine A1; D018047:Receptors, Purinergic P1; C048599:N(6)-cyclopentyladenosine; C024311:N-cyclopropyl adenosine-5'-carboxamide; D000241:Adenosine; D007608:Kainic Acid