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Chronic morphine enhances nicotine responses in single mouse enteric neurons (659.9)
Author(s) -
Gade Aravind,
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.659.9
Subject(s) - nicotine , morphine , opioid , medicine , pharmacology , μ opioid receptor , nicotinic agonist , receptor , chemistry , anesthesia
Opioids are excellent pain relievers. A major side‐effect of chronic opioid treatment is constipation whereas withdrawal following chronic exposure leads to diarrhea and increased gastrointestinal motility. These effects of chronic opioids are mediated by mu opioid receptors expressed on enteric neurons. Previous in‐vitro studies have shown that chronic opioids enhance sensitivity to nicotinic receptor agonists. In this study we examined the sensitivity to nicotine following short (10 minutes) and long‐term exposure (16‐20 hours) to morphine in isolated mouse single enteric neurons using patch‐clamp techniques. Nicotine (1mM) induced inward currents from holding potential of ‐60 mV that were significantly increased in neurons exposed for long‐term but not short‐term to morphine. However a significant shift was not seen in the EC (50) values in all neurons. The maximal current densities induced by 1mM nicotine were 168 ± 29 pA/pF, 135 ± 31 and 296 ± 51 pA/pF in control, short‐term and long‐term morphine treated cells respectively, and the EC (50) values were 44 ± 17 µM (n = 9), 42 ± 14 (n = 5) and 26 ± 7 µM (n = 11) in the same order. Shift in the maximal currents but not in the EC (50) values suggests a shift in the efficacy but not potency of nicotine after long term exposure to morphine. Studying the mechanisms involved in this enhancement is hypothesized to give a better insight into methods for treating opioid dependent and withdrawal symptoms. Supported by NIH grants DK046367 and DA024009.