Blockade of alpha 2-adrenoceptors increases opioid mu-receptor-mediated inhibition of the firing rate of rat locus coeruleus neurones.
In pontine slices of the rat brain, the frequency of spontaneous action potentials of locus coeruleus (LC) neurones was recorded extracellularly. Noradrenaline 0.1-100 mumol/l, UK 14,304 0.01-100 nmol/l, [Met5]-enkephalin 1-10,000 nmol/l and [D-Ala2,D-Leu5]enkephalin 0.1-1,000 nmol/l, all depressed the firing rate. Rauwolscine 1 mumol/l antagonized the effects of both noradrenaline and UK 14,304, but potentiated the effects of [Met5]enkephalin and [D-Ala2, D-Leu5]enkephalin. Idazoxan 1 mumol/l acted in a similar manner. Prazosin 1 mumol/l did not change the effects of either noradrenaline or [Met5]enkephalin. Naloxone 0.1 mumol/l antagonized both [Met5]enkephalin and [D-Ala2, D-Leu5]enkephalin, but failed to alter the effects of either noradrenaline or UK 14,304. Rauwolscine, idazoxan and prazosin, all 1 mumol/l, as well as naloxone 0.1 mumol/l, did not influence the firing rate when given alone. Desipramine 1 mumol/l inhibited the discharge of action potentials in a rauwolscine-antagonizable manner. Noradrenaline 10 mumol/l produced the same depression of firing, both in the presence of noradrenaline 1 mumol/l and [Met5]enkephalin 0.03 mumol/l. Likewise, the effect of [Met5]enkephalin 0.3 mumol/l was the same, irrespective of whether it was added to a medium containing [Met5]enkephalin 0.03 mumol/l or noradrenaline 1 mumol/l. The spontaneous activity of LC neurones is inhibited by somatic alpha 2-adrenoceptors and opioid mu-receptors. We suggest that the two receptors interact with each other at a site located between themselves and not in the subsequent common signal transduction system.
Illes
P
P
Department of Pharmacology, University of Freiburg, Federal Republic of Germany.
Nörenberg
W
W
D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003891:Desipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017450:Receptors, Opioid, mu
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D003891:Desipramine