The specificity of high affinity binding of avermectin B1a to mammalian brain
| Autor: | S.-S. Pong, C.C. Wang |
|---|---|
| Rok vydání: | 1980 |
| Předmět: |
Male
Cerebellum Receptors Drug Synaptic Membranes In Vitro Techniques Biology Pharmacology Disaccharides Midbrain Lactones Cellular and Molecular Neuroscience Dogs medicine Animals Binding site Receptor gamma-Aminobutyric Acid Anthelmintics Ivermectin Brain Pons Rats Kinetics medicine.anatomical_structure nervous system Biochemistry Hypothalamus Cerebral cortex Medulla oblongata Synaptosomes |
| Zdroj: | Neuropharmacology. 19:311-317 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/0028-3908(80)90155-0 |
| Popis: | Avermectin B1a, an anthelmintic with pharmacological properties of paralyzing nematodes and causing an increase in the release of GABA from rat brain synaptosomes, was found to bind to dog brain synaptosomes with an apparent-KD of 1–2 nM. This high affinity binding was saturable and the density of binding sites was estimated to be 1.54 pmol/mg protein. Results from binding competition among various analogs of the drug suggested that the binding is stereospecific and the affinities to the binding sites correlated well with the anthelmintic activities. The binding sites are unevenly distributed in the dog brain with the highest density found in cerebellum, less in midbrain, hypothalamus and cerebral cortex, and little or no binding in pons and medulla oblongata. Similar specific binding of avermectin B1a to synaptosomes of adult rat brains was also observed. The binding sites apparently emerged during the first three weeks of post-natal development of the rat brain. Although all the evidence supports the hypothesis that the binding sites may be associated with GABA synapses, the lack of competition between GABA and the drug in their bindings suggests that the drug receptors are not associated with GABA post-synaptic receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|