Presynaptic kappa-opioid receptors on noradrenergic nerve terminals couple to G proteins and interact with the alpha 2-adrenoceptors.
Stimulation-induced noradrenaline (NA) release in rabbit hippocampus is inhibited by activation of presynaptic alpha 2-adrenoceptors and kappa-opioid receptors. The purpose of the present study was to investigate (a) an interference between the alpha 2- and kappa-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 alpha 2-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 kappa-receptor agonist ethylketocyclazocine (EKC) was increased in the presence of the alpha 2-adrenoceptor antagonist yohimbine (0.1 or 1.0 microM). When autoinhibition was completely removed, EKC (1 microM) almost abolished transmitter release. Pretreatment of hippocampal tissue with either PT (8 micrograms/ml; 18 h) or N-ethylmaleimide (NEM) (30 microM; 30 min), which has been shown to alkylate PT substrates, diminished the EKC-produced inhibition of NA release. The kappa-mechanism was still impaired by these compounds when the alpha 2-receptors were blocked with yohimbine. An effect of NEM on the active site of the kappa-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 alpha 2- and kappa-opioid receptor-coupled signal transduction possibly through competition for a common pool of G proteins.
Allgaier
C
C
Institut für Pharmakologie und Toxikologie, Universität Freiburg, F.R.G.
Daschmann
B
B
Sieverling
J
J
Hertting
G
G
D000818:Animals; D001696:Biomechanical Phenomena; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D016314:Ethylketocyclazocine; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D009411:Nerve Endings / Q000378:metabolism*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D037342:Pertussis Toxin; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism* / Q000502:physiology; D017473:Receptors, Opioid, kappa; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D010566:Virulence Factors, Bordetella; D016314:Ethylketocyclazocine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D003496:Cyclazocine; D005033:Ethylmaleimide; D009638:Norepinephrine