RT Journal Article
SR Electronic
T1 Membrane potential in myenteric neurons associated with tolerance and dependence to morphine.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 15
OP 19
VO 263
IS 1
A1 J A Leedham
A1 J Q Kong
A1 D A Taylor
A1 S M Johnson
A1 W W Fleming
YR 1992
UL http://jpet.aspetjournals.org/content/263/1/15.abstract
AB Chronic treatment of guinea pigs with morphine produces subsensitivity (tolerance) of the longitudinal smooth muscle-myenteric plexus preparation to a variety of inhibitory agonists (e.g., mu opioid, alpha adrenoceptor and adenosine receptor agonists) and supersensitivity (dependence) to a variety of excitatory agonists (e.g., nicotine, 5-hydroxytryptamine and potassium ions). The present investigation was to determine if these changes in sensitivity could be related to changes in electrical properties of the S and AH neurons in the myenteric plexus. S neurons from morphine-implanted animals were significantly depolarized (7 mV) relative to those from placebo-implanted animals, whereas the membrane potential of AH neurons was unchanged. Approximately 60% of S neurons were hyperpolarized by morphine. In this subset of neurons, membranes were significantly depolarized but the threshold was unchanged in morphine-implanted animals. This means that resting potentials of S neurons from tolerant preparations are closer to threshold. The hyperpolarization produced by morphine (0.1 microM) was similar in preparations from morphine- and placebo-implanted animals. Thus, the partially depolarized state of S neurons in the myenteric plexus is the cause of the subsensitivity and supersensitivity to agonists and can explain both tolerance and dependence. Changes in opioid receptors or their coupling to potassium channels do not appear to contribute to tolerance in the longitudinal smooth muscle-myenteric plexus.