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Subclassification of release‐regulating α 2 ‐autoreceptors in human brain cortex
Author(s) -
Raiteri Maurizio,
Bonanno Giambattista,
Maura Guido,
Pende Mario,
Andrioli Gian Carlo,
Ruelle Antonio
Publication year - 1992
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.1476-5381.1992.tb13421.x
Subject(s) - prazosin , yohimbine , autoreceptor , chemistry , clonidine , mianserin , antagonist , endocrinology , agonist , rauwolscine , medicine , pharmacology , serotonin , receptor , biochemistry
1 Release‐regulating α 2 ‐autoreceptors in human brain were characterized pharmacologically in cortical slices from patients undergoing neurosurgery to remove subcortical tumours; the slices were prelabelled with [ 3 H]‐noradrenaline ([ 3 H]‐NA) and stimulated electrically (3 Hz, 2 ms, 24 mA) under superfusion conditions. 2 The stimulus‐evoked tritium overflow was almost totally Ca 2+ ‐dependent and tetrodotoxin‐sensitive. 3 Clonidine and oxymetazoline 0.01 to 1 μ m inhibited in a concentration‐dependent manner the evoked overflow of tritium. The two drugs were equipotent (EC 50 = 0.03 μ m ) and their maximal effect was approx. 45%. Phenylephrine and methoxamine, up to 1 μ m , did not affect tritium overflow. 4 Yohimbine (0.01–0.1 μ m ) shifted the concentration‐response curve of clonidine to the right. The calculated pA 2 value was 8.29. 5 Prazosin and 2‐[2‐[4‐( o ‐methoxyphenyl)piperazine‐1‐yl]ethyl]‐4,4‐dimethyl‐1,3(2H,4H)‐isoquinolinedione (AR‐C 239), tested at 0.3 μ m , did not modify the concentration‐response curve of clonidine. 6 The effect of clonidine was antagonized by (+)‐mianserin (pA 2 = 7.74), but not by up to 0.3 μ m of the (−)‐enantiomer. The concentration‐response curve of clonidine was shifted to the right by the novel α 2 ‐adrenoceptor antagonist, 5‐chloro‐4‐(1‐butyl‐1,2,5,6‐tetrahydropyridin‐3‐yl)‐thiazole‐2‐amine (Z)‐2‐butenedioate (1:1) salt (ORG 20350) (pA 2 = 7.55). 7 Yohimbine, (+)‐mianserin and ORG 20350, but not prazosin and (−)‐mianserin, increased the electrically‐evoked tritium overflow, suggesting that autoreceptors may be tonically activated by endogenous NA. 8 Desipramine (1 μ m ) increased evoked tritium overflow from human cortex slices. The effect of clonidine (0.01 − 1 μ m ) on the evoked overflow of tritium was reduced in presence of 1 μ m desipramine. 9 It is proposed that autoregulation of NA release can occur in human cerebral cortex. The process involves activation of α 2 ‐adrenoceptors which may be either the α 2A or the α 2D subtype.