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Differential effects of the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline on brain alpha 2-adrenoceptors and I2-imidazoline sites in vitro and in vivo.

Abstract：

:The alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) is a peptide-coupling agent that is being used to inactivate irreversibly alpha 2-adrenoceptors and other receptors. The aim of the present study was to assess the in vitro and in vivo effects of EEDQ on the newly discovered brain I2-imidazoline sites, located mainly in mitochondria. Preincubation of rat cortical membranes with EEDQ (10(-8)-10(-5) M) markedly decreased (20-90%) the specific binding of the selective antagonist [3H]RX821002 to alpha 2-adrenoceptors without affecting that of [3H]idazoxan (in the presence of adrenaline) to I2-imidazoline sites. In EEDQ-pretreated membranes (10(-5) M, 30 min at 25 degrees C), the density of I2-imidazoline sites (Bmax = 80 +/- 4 fmol/mg of protein) was not different from that determined in untreated membranes in the presence of (10(-6) M (-)-adrenaline (Bmax = 83 +/- 4 fmol/mg of protein), and both densities were lower (24%, p < 0.05) than the total native density of [3H]idazoxan binding sites (Bmax = 107 +/- 6 fmol/mg of protein) (I2-imidazoline sites plus alpha 2-adrenoceptors). Treatment of rats with an optimal dose of EEDQ (1.6 mg/kg, i.p., for 2 h to 30 days) reduced maximally at 6 h (by 95 +/- 1%) the specific binding of [3H]-RX821002 to alpha 2-adrenoceptors, but also the binding of [3H]idazoxan to I2-imidazoline sites (by 44 +/- 5%). Pretreatment with yohimbine (10 mg/kg, i.p.) fully protected against EEDQ-induced alpha 2-adrenoceptor inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

J Neurochem

journal_title

Journal of neurochemistry

authors

Miralles A,Ribas C,Olmos G,García-Sevilla JA

doi

10.1111/j.1471-4159.1993.tb09793.x

subject

Has Abstract

pub_date

1993-11-01 00:00:00

pages

1602-10

issue

5

eissn

0022-3042

issn

1471-4159

journal_volume

61

pub_type

杂志文章

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