δ Opioid receptor agonist, DPDPE, enhances neuronal excitability in mouse enteric nervous system (653.4)

Abstract

μ‐opioid agonists are known to inhibit gastrointestinal motility and cause constipation. But a role for the δ opioid receptor activation in propulsive motility is controversial. Previously, it was shown that μ opioid receptor agonist, morphine, decreases enteric neuron excitability via inhibition of sodium channels. Here we examined electophysiological properties by patch clamp techniques and determined the mechanism for δ opioid receptor agonist DPDPE‐induced increase in neuronal excitability in mouse single isolated enteric neurons. DPDPE (5μM) evoked spontaneous action potentials and depolarized the resting membrane potentials from ‐61.3 ± 1.3 mV to ‐52.3 ± 2.8 mV (n=3). DPDPE‐induced action potentials were reversed by ICI 174864, a δ receptor antagonist. In the presence of DPDPE, sodium channels were activated at lower membrane potentials, indicated by a leftward shift of sodium channel voltage‐dependent steady‐state activation curve. The V0.5 significantly increased from ‐28.2 ± 1.4 mV in the absence of drug to ‐37.2 ± 2.3 mV in the presence of DPDPE (n=4). We hypothesize that δ opioid receptor agonist enhances neuronal excitability by increasing sodium channel activity in mouse enteric neurons.Grant Funding Source: Supported by NIH DA024009