Adenosine A1 receptor activation mediates suppression of (-)-bicuculline methiodide-induced seizures in rat prepiriform cortex

P. H. Franklin, G. Zhang, E. D. Tripp, T. F. Murray

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The protective effects of a series of stable adenosine analogs against generalized seizures inititated by focal injection of bicuculline methiodide into the rat prepiriform cortex (PPC) were studied by microinjection of these compounds into this brain area. The adenosine agonists, 5'-N-(ethyl)carboxamido-adenosine (NECA), cyclohexyladenosine, cyclopentyladenosine, 2-chloroadenosine and R- and S-phenylisopropyladenosine (R- and S-PIA), protected animals against seizures in a dose-dependent, and extremely potent manner. NECA, the most potent compound evaluated, completely prevented seizures at doses ≥ 6.8 pmol. In contrast, heroic doses of the A2 selective ligand, 2-phenylaminoadenosine, afforded no protection against seizures. The rank order of potency of these compounds in suppressing seizures is as follows: NECA > cyclohexyladenosine > cyclopentyladenosine ≥ R-PIA > 2-chloroadenosine > S-PIA >> 2-phenylaminoadenosine. These data suggest that the antiseizure activity of these compounds in the PPC results from activation of A1 adenosine receptors. Quantitative autoradiographic analysis of the distribution of tritiated adenosine agonists 30 min after microinjection in the PPC reveals that [3H]NECA diffuses to a significantly greater extent than R-[3H]PIA, which may contribute to the relatively greater potency of the former compound in suppressing bicuculline methiodide-induced seizures. These results suggest that adenosine A1 receptors may participate in the normal inhibitory regulation of the PPC, a forebrain area which may play a significant role in the pathobiology of epilepsy.

Original languageEnglish (US)
Pages (from-to)1229-1236
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume251
Issue number3
StatePublished - Dec 1 1989
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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