Inhibition of a peripheral sympathetic-cholinergic system by presynaptic alpha 2-adrenoceptors

Intravenous administration of catecholamines produced dose-related inhibition of electrodermal responses (EDRs) evoked by electrical stimulation of the post-ganglionic sciatic nerve in anaesthetized rats, with relative potencies being (-)-adrenaline greater than (+/-)-adrenaline greater than (-)-noradrenaline = (+)-adrenaline. The suppression of EDRs by (+/-)-adrenaline and (-)-noradrenaline was blocked by pretreatment with yohimbine (0.75 mg/kg i.v.) but not by prazosin (0.3 mg/kg i.v.). The selective alpha 2-adrenoceptor agonist B-HT 920 also inhibited neurally evoked skin potential responses. This effect of B-HT 920 was antagonized by the selective alpha 2-adrenoceptor antagonist idazoxan (0.1 mg/kg i.v.) but was insensitive to prazosin. Idazoxan was more potent than yohimbine in blocking (+/-)-adrenaline-induced suppression of EDRs. Methacholine administered into the femoral artery evoked EDRs by an atropine-sensitive mechanism. Methacholine-induced EDRs were not suppressed by intravenous administration of (-)-adrenaline (1 microgram/kg or 3 micrograms/kg) whereas EDRs evoked by the sciatic nerve stimulation on the other hindpaw were inhibited. Increase in the endogenous catecholamines by asphyxia strongly inhibited EDRs by a mechanism which was also sensitive to yohimbine but not to prazosin. These results suggest that peripheral presynaptic alpha 2-adrenergic mechanisms are involved in inhibition of transmitter release in this sympathetic-cholinergic system.