Morphine produces a multiphasic effect on the release of substance P from rat trigeminal nucleus slices by activating different opioid receptor subtypes

Abstract

Morphine (MOR) produces a concentration-dependent multiphasic effect (inhibitions and facilitations) on K +-eviked substance P (SP) release from rat trigeminal nucleus slices 47. 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 μ 1-opioid receptor antagonist naloxonazine (1 nM). MOR at 100 nM elicited an increase in SP release which was abolished selectively by the μ-opioid receptor antagonist, β-funaltrexamine (β-FNA; 20 nM) and attenuated by the σ-opioid receptor antagonist, ICI 174,864 (0.3 μM). 3 μM MOR produced an inhibition of SP release that was reversed only by ICI 174,864 (0.3 μM). MOR at even higher concentrations (30 μM) produced an enhancement of SP release that was reversed selectively by 3 nM n-binaltorphimine (n-BNI; 3 nM), a κ-opioid receptor antagonist. In slices pretreated with 20 nM β-FNA and in the presence of 0.3 μM ICI 174,864 (μ- and σ-opioid receptor blockade), both 100 nM and 3 μM 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 β-FNA-sensitive μ- and excitatory σ-opioid receptors whereas the facilitation of SP release induced by 30 μM MOR could be due to the activation of κ-opioid receptors. 1 nM and 3 μM MOR may inhibit SP release by stimulating naloxonazine-sensitive μ 1- and inhibitory σ-opioid receptors, respectively.