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Central α 2 ‐autoreceptors: agonist dissociation constants and recovery after irreversible inactivation
Author(s) -
Agneter E.,
Drobny H.,
Singer E.A.
Publication year - 1993
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.1476-5381.1993.tb12811.x
Subject(s) - autoreceptor , agonist , chemistry , dissociation constant , partial agonist , clonidine , receptor , biophysics , intrinsic activity , endocrinology , medicine , dissociation (chemistry) , pharmacology , biochemistry , biology
1 Rats received an intraperitoneal injection of 1.6 mg kg −1 N‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline (EEDQ) to achieve an irreversible inactivation of presynaptic release‐modulating α 2 ‐autoreceptors. Cerebral cortex slices were prepared at different times after the injection (24, 48, 96, 192, 336, 774 h), incubated with [ 3 H]‐noradrenaline ([ 3 H]‐NA), superfused and stimulated electrically with 4 pulses at 100 Hz (= autoinhibition‐free condition). Overflow of radioactivity was used to measure release. Furchgott analysis was used to estimate agonist dissociation constants ( K A ) and pool size of resynthesized receptors (q). 2 The K A values of the three α 2 ‐autoreceptor agonists, bromoxidine (UK‐14304), clonidine and noradrenaline (NA) were 187 n m , 72 n m , and 1202 n m , respectively. 3 The release‐inhibiting effects of the agonists returned considerably faster than the receptor pool. The calculated half‐lives for the recovery of the maximal release‐inhibiting effects of bromoxidine, clonidine and NA were 30.7, 63.6 and 20.8 h, respectively, whereas the half‐life for the recovery of the receptor pool was 445 h. 4 The data indicate a large receptor reserve at presynaptic α 2 ‐autoreceptors for the agonists used and validate the use of EEDQ as a tool for the determination of agonist dissociation constants.