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Monensin inhibits the binding of 3 H‐flunitrazepam to and reveals the intracellular passage of GABA A /benzodiazepine receptor
Author(s) -
Yin Hsiang Shu
Publication year - 1992
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240490209
Subject(s) - monensin , receptor , intracellular , gabaa receptor , flunitrazepam , chemistry , biochemistry , golgi apparatus , biology , microbiology and biotechnology , cell
Effects of monensin were examined on the intracellular processing of the GABA A /benzodiazepine receptor (GABA A /BZDR) in neuron cultures derived from embryonic chicken brain, using 3 H‐flunitrazepam as the probe for the benzodiazepine modulator site on the receptor. Incubation of cultures with 0.1 or 1 μM monensin for 3 h blocked the binding of 3 H‐flunitrazepam by about 18%. Loss of ligand binding was due to a reduction in the number of binding sites, with no significant changes in receptor affinity. The general cellular protein synthesis and glycosylation in the cells were inhibited by 26% and 56%, respectively, in the presence of 1 μM monensin, as detected by assaying the incorporation of 3 H‐leucine and 3 H‐galactose. In contrast, an increase was observed for mannose incorporation by the cultures in the presence of the drug. Moreover, the results from in situ trypsinization of the cultures following monensin treatment showed that monensin did not alter the distribution of intracellular and surface receptors. The data suggest that monensin induces the down‐regulation of GABA A /BZDR by generating abnormal glycosylation of the receptor and interrupting its transport within the Golgi apparatus, as well as from the Golgi apparatus to the intracellular pool and cell membrane. The galactosylation of receptor proteins may be important for the maturation of the receptor.