Cherubini_1988_J.Pharmacol.Exp.Ther_247_830

Guinea pigs were treated chronically with morphine by implantation of pellets and the ileum was later removed for experiments in vitro. Intracellular recording from myenteric neurons showed that chronic morphine treatment led to the development of an increased calcium-dependent afterhyperpolarization, whether this followed an action potential or the depolarization resulting from activation of nicotinic acetylcholine receptors. The properties of the neurons were otherwise normal. Naloxone depolarized about one-third of neurons and led to the appearance of spontaneous fast excitatory postsynaptic potentials in many cells. Extracellular recordings from neurons induced to fire with suction electrodes showed that the excitation caused by naloxone was prevented in solutions that contained sufficient cobalt to block synaptic transmission. Measurements of longitudinal muscle tension of intact pieces of ileum showed that the contracture caused by naloxone was much reduced by prior exposure of the ileum in vitro for 30 min to beta-funaltrexamine. The beta-funaltrexamine appeared to have irreversibly blocked a significant fraction of the mu receptors because the effectiveness of Tyr-D-Ala-Gly-MePhe-Gly-ol to inhibit nerve-evoked contractile responses (twitches) was much reduced in tissues treated with beta-funaltrexamine. These results indicate that at least a portion of the contracture results from an action of naloxone at kappa rather than mu receptors.(ABSTRACT TRUNCATED AT 250 WORDS)