Actions of morphine on noradrenaline efflux in the rat locus coeruleus are mediated via both opioid and alpha 2 adrenoceptor mechanisms.
A recent report showed that morphine inhibited [3H]clonidine binding to human platelet alpha 2 receptors. As the analgesic effects of morphine and clonidine are clinically additive, we investigated the possibility that morphine might stimulate alpha 2 receptors or alpha 2 mechanisms in rat locus coeruleus (LC) slices. Stimulated LC noradrenaline efflux was measured by fast cyclic voltammetry. Cumulatively applied morphine 10(-8)-10(-4) mol litre-1 had no effect on noradrenaline efflux evoked by pseudo-single-pulse stimulations (20 pulses at 100 Hz) while the alpha 2 agonist dexmedetomidine 2 x 10(-10)-10(-7) mol litre-1 decreased efflux of noradrenaline in a concentration-dependent manner. Administration of single concentrations of morphine 10(-6)-10(-4) mol litre-1 significantly decreased efflux of noradrenaline (by 22% and 17%, respectively) and attenuated the effect of dexmedetomidine in a concentration-dependent fashion. Morphine 10(-6)-10(-4) mol litre-1 also decreased efflux of noradrenaline on long stimulus trains (50 pulses at 50 Hz). These data suggest that the analgesic potentiation of alpha 2 and opioid agonists is not mediated via LC alpha 2 receptors.
Jorm
C M
CM
Anaesthetics Unit (Neurotransmission Laboratory), London Hospital Medical College, Royal London Hospital, Whitechapel.
Stamford
J A
JA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D020926:Medetomidine; D009020:Morphine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; D011957:Receptors, Opioid; D009020:Morphine; D020926:Medetomidine; D009638:Norepinephrine