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Depolarization‐induced release of propranolol and atenolol from rat cortical synaptosomes
Author(s) -
Bright Patricia S.,
Gaffney Thomas E.,
Street James A.,
Webb Jerry G.
Publication year - 1985
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.1476-5381.1985.tb12934.x
Subject(s) - atenolol , propranolol , veratridine , depolarization , tetrodotoxin , chemistry , synaptosome , biophysics , pharmacology , membrane potential , endocrinology , medicine , sodium , membrane , biochemistry , sodium channel , biology , organic chemistry , blood pressure
1 The accumulation and release of [ 3 H]‐propranolol and [ 3 H]‐atenolol were examined in synaptosomes from rat cerebral cortex. 2 Synaptosomes accumulated 20 pmol propranolol and 0.6 pmol atenolol mg −1 protein when incubated at 30°C with radiolabeled drugs (0.1 μ m ). 3 Exposure of propranolol‐loaded synaptosomes to elevated K + , Rb + or Cs + evoked a concentration‐dependent increase in propranolol efflux. The action of these ions in releasing propranolol was highly correlated with their ability to produce synaptosomal membrane depolarization, as estimated with the voltage‐sensitive dye diS‐C 3 ‐(5). 4 Elevated K + also promoted atenolol release from synaptosomes in a concentration‐dependent manner. 5 Veratridine (10 μ m ) released propranolol and atenolol from synaptosomes and these effects were antagonized by tetrodotoxin (1 μ m ). 6 Under Ca 2+ ‐free conditions, K + ‐induced release of propranolol was reduced by 37% and atenolol release was diminished by 68%. 7 The results support the concept that both polar and non‐polar β‐adrenoceptor blocking drugs may be accumulated by nerve endings for release by membrane depolarization and suggest that neural storage and release of these molecules may influence their concentrations at localized sites of action.