In vivo tonic inhibition of spinal substance P (-like material) release by endogenous opioid(s) acting at delta receptors.
Although numerous data support the existence of a presynaptic inhibitory control by opioids of substance P-containing primary afferent fibres entering the dorsal horn of the spinal cord, the exact nature of the opioid receptor involved in this control is still a matter of debate. In the present study, the potential role of delta opioid receptors was investigated by looking for the possible effects of selective delta ligands on the in vivo release of substance P-like material from the whole spinal cord in halothane-anaesthetized rats. Perfusion of the intrathecal space allowed the collection of substance P-like material that was released at a constant rate of approximately 0.65 pg substance P equivalents/min for at least 135 min. The addition of Tyr-D-Thr-Gly-Phe-Leu-Thr (10 microM) or dermenkephalin (10 microM), two selective delta agonists, to the perfusing fluid produced a marked reduction (-50-65%) in substance P-like material outflow which could be prevented by the selective delta antagonist naltrindole (10 microM) but not by naloxone (10 microM), which acts preferentially on mu opioid receptors. Furthermore, naltrindole alone (or the association of this antagonist plus dermenkephalin) enhanced the outflow of substance P-like material (+ 170%) as expected from the blockade of a tonic inhibitory control due to the stimulation of delta receptors by endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS)
Collin
E
E
INSERM U288, Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médecine, Paris, France.
Mauborgne
A
A
Bourgoin
S
S
Chantrel
D
D
Hamon
M
M
Cesselin
F
F
D000595:Amino Acid Sequence; D000818:Animals; D003864:Depression, Chemical; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D008969:Molecular Sequence Data; D009019:Morphinans / Q000008:administration & dosage / Q000494:pharmacology; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives*; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D017465:Receptors, Opioid, delta; D012636:Secretory Rate / Q000187:drug effects; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
D007211:Indoles; D009019:Morphinans; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C059567:deltorphin; D013373:Substance P; D009270:Naloxone; D009271:Naltrexone; C037653:deltakephalin; C055382:naltrindole