Suppression of the nicotinic acetylcholine response in rat superior cervical ganglionic neurons by steroids

The effects of various types of steroids on the nicotinic acetylcholine (AC h) receptor (nAChR)-mediated responses were investigated in superior cervic al ganglionic neurons acutely dissociated from rats using nystatin perforat ed patch recording. ACh induced a peak followed by a gradual decrease in th e inward current at a holding potential of -40 mV. Nicotine, but not muscar ine, mimicked ACh. Hydrocortisone at a concentration of >10(-6) M reversibl y suppressed both the peak and steady-state nicotine-induced currents (I-nl c) in a noncompetitive manner. The inhibition of I-nlc by hydrocortisone di d not show any voltage dependency and persisted in the presence of either c yclic AMP modulators, forskolin and 3-isobutyl-1-methylxanthine, or a prote in kinase A inhibitor, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide d ihydrochloride (H-89). beta-Estradiol, androsterone, aldosterone, and 17 al pha-estradiol mimicked hydrocortisone in its inhibitory action on ACh-induc ed currents (I-ACh). The potency for the inhibitory actions on I-ACh was as follows: androsterone > beta-estradiol > hydrocortisone greater than or eq ual to aldosterone = 17 alpha-estradiol. Cholesterol had no effect on the I -ACh. In conclusion, the structural characteristics of a steroid are thus c onsidered to be necessary to block nicotinic I-ACh in rat superior cervical ganglionic cells, whereas the cholesterol side chain might disturb the inh ibitory action of the steroid skeleton on nAChRs.