Premium
δ Opioid receptor agonist, DPDPE, enhances neuronal excitability in mouse enteric nervous system (653.4)
Author(s) -
Hashimoto Atsushi,
Dewey William,
Akbarali Hamid
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.653.4
Subject(s) - agonist , chemistry , sodium channel , opioid receptor , receptor , enteric nervous system , opioid , pharmacology , patch clamp , neuron , endocrinology , medicine , neuroscience , sodium , biology , biochemistry , organic chemistry
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 V 0.5 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