Morphine produces a multiphasic effect on the release of substance P from rat trigeminal nucleus slices by activating different opioid receptor subtypes.
Morphine (MOR) produces a concentration-dependent multiphasic effect (inhibitions and facilitations) on K(+)-evoked substance P (SP) release from rat trigeminal nucleus slices. In this study, we tested the action of selective opioid receptor antagonists on this multiphasic effect of MOR. 1 nM MOR produced an inhibition of K(+)-evoked release of SP that was affected only by the selective mu 1-opioid receptor antagonist naloxonazine (1 nM). MOR at 100 nM elicited an increase in SP release which was abolished selectively by the mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA; 20 nM) and attenuated by the delta-opioid receptor antagonist, ICI 174,864 (0.3 microM). 3 microM MOR produced an inhibition of SP release that was reversed only by ICI 174,864 (0.3 microM). MOR at even higher concentrations (30 microM) produced an enhancement of SP release that was reversed selectively by 3 nM n-binaltorphimine (n-BNI; 3 nM), a kappa-opioid receptor antagonist. In slices pretreated with 20 nM beta-FNA and in the presence of 0.3 microM ICI 174,864 (mu- and delta-opioid receptor blockade), both 100 nM and 3 microM MOR elicited a strong facilitation of K(+)-evoked SP release which was sensitive to 3 nM n-BNI. Thus, the increase in SP release produced by 100 nM may be mediated by the simultaneous stimulation of beta-FNA-sensitive mu- and excitatory delta-opioid receptors whereas the facilitation of SP release induced by 30 microM MOR could be due to the activation of kappa-opioid receptors. 1 nM and 3 microM MOR may inhibit SP release by stimulating naloxonazine-sensitive mu 1- and inhibitory delta-opioid receptors, respectively.
Suarez-Roca
H
H
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7455.
Maixner
W
W
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009292:Narcotic Antagonists; D011188:Potassium / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D013373:Substance P / Q000378:metabolism*; D014276:Trigeminal Nerve / Q000187:drug effects / Q000378:metabolism*
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D013373:Substance P; D009020:Morphine; D011188:Potassium