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Presynaptic K ‐Opioid Receptors on Noradrenergic Nerve Terminals Couple to G Proteins and Interact with the α 2 ‐Adrenoceptors
Author(s) -
Allgaier Clemens,
Daschmann Beate,
Sieverling Jens,
Hertting Georg
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb08561.x
Subject(s) - yohimbine , receptor , stimulation , g protein , endocrinology , agonist , pertussis toxin , opioid receptor , medicine , chemistry , opioid , biophysics , biology , antagonist , biochemistry
Stimulation‐induced noradrenaline (MA) release in rabbit hippocampus is inhibited by activation qf presynaptic α 2 ‐adrenoceptors and k ‐opioid receptors. The purpose of the present study was to investigate (a) an interference between the α 2 ‐ 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 α 2 ‐receptors. [ 3 H]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 α 2 ‐adrenoceptor antagonist yohimbine (0.1 or 1.0 μ M). When autoinhibitionn was completely removed, EKC (1 μ M) 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 α 2 ‐ 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 α 2 ‐ and k ‐opioid receptor‐coupled signal transduction possibly through competition for a common pool of G proteins.