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Covariation of α 2 ‐adrenoceptor density and function following irreversible antagonism with EEDQ
Author(s) -
Durcan Michael J.,
Morgan Philip F.,
Etten Michelle L.,
Linnoila Markku
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13158.x
Subject(s) - antagonism , function (biology) , chemistry , neuroscience , medicine , pharmacology , endocrinology , biology , receptor , microbiology and biotechnology
1 Administration of the irreversible antagonist, N‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline, (EEDQ, 2 mg kg −1 , i.p.) to mice reduced binding of [ 3 H]‐RX 821002 (2‐methoxy‐idazoxan) to α 2 ‐adrenoceptors in whole mouse brain by 75% 24 h later. The receptor binding returned over time only being reduced by 25% by 16 days post administration; the time taken for binding to return to 50% of control levels was estimated to be 5.25 days. 2 EEDQ administration also resulted in the loss of the sedative effect of the α 2 ‐adrenoceptor agonist, medetomidine, measured by the holeboard test of directed exploration and locomotor activity. Agonistinduced sedation returned to control values by 8 days post EEDQ administration. 3 EEDQ administration also resulted in the loss of the hypothermic response to medetomidine (0.1 mg kg −1 , i.p.). Medetomidine‐induced hypothermia returned to control values by 12 days post EEDQ administration. 4 Pretreatment with the selective α 2 ‐adrenoceptor antagonist, RX 821002 (0.1–3.0 mg kg −1 , i.p.) 45 min before EEDQ prevented the loss of α 2 ‐adrenoceptors as well as the blockade of medetomide‐induced sedation and hypothermia by EEDQ. 5 The results of these experiments indicate that there is significant receptor reserve for α 2 ‐adrenoceptor‐mediated behavioural and physiological responses.