AJP - Cell Physiology, Vol 257, Issue 5 C906-C912, Copyright © 1989 by American Physiological Society
Glucocorticoids inhibit acetylcholine-induced current in chromaffin cells
M. Inoue and H. Kuriyama
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
The effects of dexamethasone, a synthetic glucocorticoid, on membrane
excitability and on the acetylcholine (ACh)-induced inward current (IACh)
were studied in dispersed guinea pig adrenal medullary cells by using the
whole cell version of the patch-clamp technique. Bath application of 10
microM dexamethasone had no effect on the resting membrane conductance or
voltage-gated Na+, Ca2+, or K+ channels, whereas it reversibly inhibited
the IACh at a holding potential of -70 mV. Intracellular application of
dexamethasone through the patch electrode did not modify the IACh.
Application of 10 microM dexamethasone neither shifted the dose-response
curve of the peak IACh to the right [dissociation constant (Kd) = 50
microM] nor affected its Hill coefficient (1.2) but inhibited the current
amplitudes by approximately 41% in the cells sufficiently pretreated with
dexamethasone. Furthermore, fractional inhibition of the IACh at the end of
approximately 50-s application was the same for any concentration of ACh
(3-100 microM). The dose-response curve of the inhibition by dexamethasone
showed a good fit to the theoretical line assuming an inhibition constant
(Ki) of 10 microM and a Hill coefficient of 1. Hydrocortisone
21-hemisuccinate sodium salt (25 microM) and prednisolone 21-hemisuccinate
sodium salt (25 microM) inhibited the IACh to a lesser extent than 25
microM dexamethasone. These results suggest that dexamethasone binds to the
specific site on the outer cell membrane, probably on the ACh
receptor-coupled channel, and inhibits the IACh in a noncompetitive manner,
thus controlling the immediate catecholamine release from the adrenal
medulla.
