Premium
Rapid, agonist‐induced desensitization of α 2 ‐autoreceptors modulating transmitter release
Author(s) -
Boehm Stefan,
Huck Sigismund,
Schwarz Karin,
Agneter Ernst,
Drobny Helmut,
Singer Erast A.
Publication year - 1995
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.1476-5381.1995.tb13326.x
Subject(s) - autoreceptor , agonist , endocrinology , stimulation , medicine , desensitization (medicine) , inhibitory postsynaptic potential , chemistry , receptor , biology
1 The release of previously incorporated [ 3 H]‐noradrenaline was investigated in cultures of dissociated chick or rat sympathetic neurones and in cerebrocortical slices from neonatal or adult rats. Noradrenaline, in the presence of 10 μmol l −1 of the uptake inhibitor, cocaine, or the selective α 2 ‐adrenoceptor agonist, 5‐bromo‐ N ‐(4,5‐dihydro‐1 H ‐imidazol‐2‐yl)‐6‐quinoxalinamine (UK 14,304), was applied for different periods of time in order to detect a possible time‐dependence of the α 2 ‐adrenoceptor‐mediated inhibition of electrically evoked tritium outflow. 2 In chick sympathetic neurones, stimulation‐evoked overflow was reduced to 30%, 42%, or 56% of control when noradrenaline (1 μmol l −1 ) was present for 2, 8, or 16 min, respectively. Likewise, UK 14,304 (1 μmol l −1 ) present for these periods of time reduced 3 H overflow to 35%, 51%, and 53% of control, respectively. Addition of 1 nmol l −1 to 10 μmol l −1 UK 14,304 for either 2 or 16 min did not produce significantly different IC 50 values, but the inhibitory effects were smaller with 16 min as compared to 2 min exposure at concentrations ≥ 10 nmol l −1 . 3 In rat sympathetic neurones, noradrenaline (100 nmol l −1 ) reduced stimulation‐evoked overflow to 33%, 56%, or 57% of control, when present for 2, 8, or 16 min, respectively. Addition of UK 14,304 (1 μmol l −1 ) for these periods of time caused inhibition to 11%, 41%, and 46% of control. Applying UK 14,304 for either 2 or 16 min did not result in significantly different IC 50 values, but the inhibition induced by 16 min as compared to 2 min exposure was smaller at concentrations ≥ 10 nmol l −1 . 4 In cerebrocortical slices from either neonatal or adult rats, exposure to 0.1 to 1.0 μmol l −1 UK 14,304 for 16 min never caused a smaller inhibition than a corresponding 3 min exposure, although various experimental conditions were investigated. 5 The results demonstrate that α 2 ‐adrenoceptors which regulate noradrenaline release from sympathetic neurones undergo agonist‐induced desensitization within minutes. Such rapid desensitization of α 2 ‐autoreceptors was not detected in brain slice preparations.