Presynaptic K‐Opioid Receptors on Noradrenergic Nerve Terminals Couple to G Proteins and Interact with the α2‐Adrenoceptors

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Abstract
Stimulation-induced noradrenaline (MA) release in rabbit hippocampus is inhibited by activation qf presynaptic α2-adrenoceptors and k-opioid receptors. The purpose of the present study was to investigate (a) an interference between the α2- and k-mechanisms, and (b) a coupling of the opioid receptors to pertussis toxin (PT)-sensitive guanine nucleotide-binding proteins (G proteins), as has been previously shown for the α2-receptors. [3H]NA release from hippocampal slices was evoked by electrical field stimulation (360 pulses/3 Hz). Inhibition of stimulation-evoked NA release by the preferential K-receptor agonist ethylketocyclazocine (EKC) was increased in the presence of the α2-adrenoceptor antagonist yohimbine (0.1 or 1.0 μM). When autoinhibitionn was completely removed, EKC (1 μM) almost abolished transmitter release. Pretreatment of hippocampal tissue wiih either PT (8 μg/ml; 18 h) or N-ethylmaleimide (NEM) (30 μM; 30 min), which has been shown to alkylate PT substrates, diminished the EKC-produced inhibition of NA release. The K-mecha-nism was still impaired by these compounds when the α2- receptors were blocked with yohimbine. An effect of NEM on the active site of the K-receptor seems to be unlikely, because NEM diminished the EKC-induced inhibition of release irrespective of whether or not the opioid receptor was occupied by EKC during exposure to NEM. The present results suggest an interference of both α2- and k-opioid receptor-coupled signal transduction possibly through competition for a common pool of G proteins.