2P044 Inhibition of nicotinic ACh response by steroids in rat parasympathetic airway ganglion neurons

The effects of various steroids on acetylcholine (ACh)-induced current were studied in the neurons acutely isolated from the rat airway parasympathetic ganglia using nystatin perforated-patch recording configuration. At a holding potential of -40 mV, ACh evoked slow and fast inward currents via muscarinic M1 and α-bungarotoxin-insensitive nicotinic receptors, respectively. Hydrocortisone markedly inhibited the current activated via nicotinic ACh receptor. Under the conditions that muscarinic response was inhibited, hydrocortisone inhibited the current induced by 3x10^-5 M ACh with a half maximum inhibitory concentration (IC50) of 2.1x10^-4M. This inhibitory effect was voltage-independent. Hydrocortisone suppressed the maximum response of the ACh concentration-response curve, indicating that the inhibitory action of hydrocortisone on the nicotinic ACh response is non-competitive. The nicotinic ACh response was also inhibited by other steroids including androsterone, aldosterone, β-estradiol and pregrenolone. The results suggests that steroids may reduce the ACh release from the vagal nerve terminal in the airway by reducing the ganglionic transmimssion. This action could be expecited to be a beneficial action in asthma, since cholinergic bronchoconstriction may be important in airway obstruction.