Opioid effects on spinal [3H]5-hydroxytryptamine release are not related to their antinociceptive action.
Several opioid compounds were evaluated for an ability to modulate the K(+)-stimulated release of [3H]serotonin ([3H]5-hydroxytryptamine, [3H]5-HT) from rat spinal cord synaptosomal and tissue slice preparations. Selective kappa-opioid receptor agonists depressed K(+)-stimulated release of the radiolabelled transmitter from both tissue preparations, an effect which was reversed by norbinaltorphimine. Conversely, the selective mu- and delta-opioid receptor agonists [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO) and [D-Pen2,D-Pen5]enkephalin (DPDPE), respectively, enhanced the K(+)-stimulated release of [3H]5-HT. This effect was only seen using the tissue slice preparation. When used at concentrations near its reported Kd for mu-opioid receptors, the selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) blocked the action of DAMGO, but had no effect on the action of DPDPE. However, higher concentrations of CTOP, as well as all effective concentrations of selective delta-opioid receptor antagonists, blocked the action of both DAMGO and DPDPE. All agonist effects on spinal 5-HT release, regardless of the tissue preparation, were only seen at high (microM) concentrations. Moreover, effects of the opioid agonists were not consistent with the reported involvement of spinal 5-HT neurotransmission in the mediation of their antinociceptive action. Thus, the ability of opioids to modulate spinal 5-HT release appears to be of minimal physiological significance.
Monroe
P J
PJ
Department of Anesthesiology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506-9134.
Kradel
B K
BK
Smith
D L
DL
Smith
D J
DJ
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D066298:In Vitro Techniques; D007553:Isotope Labeling; D008297:Male; D008969:Molecular Sequence Data; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D012701:Serotonin / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000700:Analgesics; D004745:Enkephalins; D009294:Narcotics; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D012701:Serotonin; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-; D011188:Potassium