Inhibition by pregnenolone sulfate of nicotinic acetylcholine response in adrenal chromaffin cells
| Autor: | Eiichi Tachikawa, Kenzo Kudo, Takeshi Kashimoto |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Nicotine
medicine.medical_specialty Chromaffin Cells Receptors Nicotinic Tritium chemistry.chemical_compound Catecholamines Internal medicine medicine Animals Cells Cultured Acetylcholine receptor Pharmacology Dose-Response Relationship Drug Sodium Acetylcholine Competitive Bidding Nicotinic acetylcholine receptor Endocrinology Nicotinic agonist medicine.anatomical_structure chemistry Adrenal Medulla Pregnenolone Chromaffin cell Catecholamine Calcium Cattle Pregnenolone sulfate medicine.drug |
| Zdroj: | European Journal of Pharmacology. 456:19-27 |
| ISSN: | 0014-2999 |
| Popis: | To evaluate whether pregnenolone sulfate, an abundant neurosteroid in the brain, modulates nicotinic receptor-mediated responses, the effect of pregnenolone sulfate on acetylcholine-induced catecholamine secretion was investigated in cultured bovine adrenal chromaffin cells. Pregnenolone sulfate inhibited acetylcholine-induced catecholamine secretion (IC(50): 27 microM). In addition, pregnenolone sulfate inhibited acetylcholine-induced Na(+) (IC(50): 12 microM) and Ca(2+) (IC(50): 20 microM) influxes. However, pregnenolone sulfate did not inhibit either catecholamine secretion or Ca(2+) influx stimulated by high K(+). Binding of [3H]nicotine to nicotinic receptors was not altered by pregnenolone sulfate. The inhibitory effect on the acetylcholine-induced secretion was insurmountable by increasing acetylcholine concentrations, but was enhanced by decreasing external Na(+) concentrations. These results suggest strongly that pregnenolone sulfate noncompetitively inhibits nicotinic receptor-operated ion channels, thereby suppressing Na(+) influx through the channels and, consequently, attenuates both Ca(2+) influx and catecholamine secretion. Our results further indicate that pregnenolone sulfate may modulate nicotinic receptor-mediated responses in the brain. |
| Databáze: | OpenAIRE |
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