Summary
Previous studies have shown that a low dose of the alkylating compound N-ethoxycarbonyl-2-ethoxy1,2-dihydroquinoline (EEDQ) reduces the density of α2-adrenoceptors in rat cerebral cortex and antagonizes the effects of an α2-adrenoceptor agonist on noradrenaline release in rat cortical slices. In the present study, a corresponding dose of EEDQ (1 mg/kg, s. c., 24 h) was shown to reduce the effect of the α2-adrenoceptor agonists clonidine and guanfacine on noradrenaline turnover in rat brain while not affecting the inhibitory effect of clonidine on locus coeruleus (LC) cell firing. When considerably higher doses of EEDQ were administered (10 and 20 mg/kg, s. c., 24 h) not only the biochemical but also the electrophysiological effects of clonidine were markedly reduced (or even reversed). The data support the notion that EEDQ decreases the responsiveness of brain α2-adrenergic receptors; moreover, they indicate that α2-adrenoceptors regulating LC activity are characterized by a larger receptor reserve or are less sensitive to the influence of alkylation than are the population of α2-adrenoceptors regulating noradrenaline utilization.
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Engberg, G., Eriksson, E. Effects of α2-adrenoceptor agonists on locus coeruleus firing rate and brain noradrenaline turnover in N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-treated rats. Naunyn-Schmiedeberg's Arch Pharmacol 343, 472–477 (1991). https://doi.org/10.1007/BF00169548
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DOI: https://doi.org/10.1007/BF00169548