PMID: 11918848Mar 29, 2002Paper

Modulation of neuronal nicotinic acetylcholine receptors by glucocorticoids

Acta Pharmacologica Sinica
Li-Jun ShiChun-An Wang

Abstract

To investigate the nongenomic effect of the glucocorticoid corticosterone on nicotinic acetylcholine receptor (nAChR) in PC12 cells. The acetylcholine (ACh)-induced current was measured on nerve growth factor differentiated PC12 cells using whole-cell patch-clamp techniques. The ACh-induced current (IACh) proved to be generated through neuronal nAChR. When ACh (30 micromol/L) was applied simultaneously with corticosterone (0.1 - 10 micromol/L), the decay of IACh was faster with slight inhibition on the peak current amplitude. Pretreating PC12 cells with corticosterone augmented the inhibition on the peak IACh and did not alter receptor desensitization. Bovine serum albumin-conjugated corticosterone (0.1 - 10 micromol/L) had the inhibition similar to corticosterone. The rapid effect induced by corticosterone was reversible, concentration-dependent, and voltage-independent. Corticosterone has rapid inhibitory effect on IACh, which is mediated by a nongenomic mechanism. It indicates that corticosterone binds to the specific site on the outer cell membrane, probably on the neuronal nicotinic receptor-coupled channel, and inhibits the IACh in a noncompetitive manner, thus controlling the immediate catecholamine release from the symp...Continue Reading

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