| ID | 32 |
|---|---|
| Name | glycine receptor (protein family or complex) |
| Synonyms | Glycine receptor; Glycine receptors |
| ID | 1478 |
|---|---|
| Name | alpha-endosulfan |
| CAS | (3α,5aβ,6α,9α,9aβ)-6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepin 3-oxide |
| PubMed | Abstract | RScore(About this table) |
|---|---|---|
| 12614680 | Vale C, Fonfria E, Bujons J, Messeguer A, Rodriguez-Farre E, Sunol C: The organochlorine pesticides gamma-hexachlorocyclohexane (lindane), alpha-endosulfan and dieldrin differentially interact with (A) and -gated channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. The organochlorine pesticides gamma-hexachlorocyclohexane, alpha-endosulfan and dieldrin induce in mammals a hyperexcitability syndrome accompanied by convulsions. They reduce the -induced Cl (-) flux. The strychnine-sensitive glycine receptor also regulates Cl (-)-flux inhibitory responses. We studied the effects of these compounds on Cl (-) channels associated with glycine receptors in cultured cerebellar granule cells in comparison to the (A) receptor. Both (EC (50): 5 microM) and (EC (50): 68 microM) increased (36) Cl (-) influx. This increase was antagonized by bicuculline and strychnine, respectively. Lindane inhibited with similar potency both (A) (IC (50): 6.1 microM) and (5.0 microM) receptors. alpha-Endosulfan and dieldrin inhibited the (A) receptor (IC (50) values: 0.4 microM and 0.2 microM, respectively) more potently than the glycine receptor (IC (50) values: 3.5 microM and 3 microM, respectively). Picrotoxinin also inhibited the glycine receptor, although with low potency (IC (50)> 100 microM). A 3D pharmacophore model, consisting of five hydrophobic regions and one bond acceptor site in a specific three-dimensional arrangement, was developed for these compounds by computational modelling. We propose that the bond acceptor moiety and the hydrophobic region were responsible for the affinity of these compounds at the (A) receptor whereas only the hydrophobic region of the molecules was responsible for their interaction with the glycine receptors. In summary, these compounds could produce neuronal hyperexcitability by blocking glycine receptors besides the (A) receptor. We propose that two zones of the polychlorocycloalkane pesticide molecules (a lipophilic zone and a polar zone) differentially contribute to their binding to (A) and glycine receptors. |
87(1,1,1,7) |