Effects of veratridine and high potassium on μ-opioid receptor internalization in the rat spinal cord: Stimulation of opioid release versus inhibition of internalization

Abstract

Veratridine and high K +-induced μ-opioid receptor (MOR) internalization in rat spinal cord slices by evoking opioid release. Veratridine induced up to 75% MOR internalization but showed an atypical concentration–response: its effect increased steeply from 5 μM to 10 μM, and declined thereafter to disappear at 100 μM. At 100 μM, veratridine also inhibited of MOR internalization induced by exogenous endomorphin-2. This inhibition was caused by Na + entry, since the Na + ionophore monensin (50 μM) also inhibited endomorphin-induced MOR internalization. In contrast, veratridine induced neurokinin 1 receptor internalization (by evoking substance P release) without any inhibition at high concentrations. KCl evoked up to 80% MOR internalization, which disappeared in the presence of lidocaine or in the absence of peptidase inhibitors, indicating that it involved neuronal firing and peptide release. Unlike veratridine, KCl did not inhibit MOR internalization at high concentrations. However, both KCl and veratridine evoked more MOR internalization when applied for 2 min than for 20 min because of a direct inhibition of MOR internalization with the longer incubation times. These results show that short incubations with 20 μM veratridine or 30 mM KCl are optimal stimuli to evoke opioid release and MOR internalization in the spinal cord.