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 slices47. 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-mu-M). 3-mu-M MOR produced an inhibition of SP release that was reversed only by ICI 174,864 (0.3-mu-M). MOR at even higher concentrations (30-mu-M) 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-mu-M ICI 174,864 (mu- and delta-opioid receptor blockade), both 100 nM and 3-mu-M 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-mu-M MOR could be due to the activation of kappa-opioid receptors. 1 nM and 3-mu-M MOR may inhibit SP release by stimulating naloxonazine-sensitive mu-1- and inhibitory delta-opioid receptors, respectively.