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Gintzler AR. 
“Interactions Among Narcotics, Neurotransmitters, and phosphodiesterase Inhibitors in the Guinea Pig Ileum: A Hypothesis on the Mechanism of Action of Narcotics.”. 
Dissertation Abstr Intern B. 1975;35(7):3488.
The effects of 5-HT on the inhibitory response of the guinea-pig ileum to morphine -were studied. Concentrations of 5-HT ranging from 2 x 10-8 to 2 x 10-7 M potentiate the inhibitory effects of morphine. Small concentrations of morphine- (10 M) potentiate the inhibitory response to 5-HT. Both of these effects are abolished by washing. This potentiation is also seen with both nalorphine and methadone, and seems to be due to a specific interaction between 5-HT and narcotic analgesics. Similar concentrations of 5-HT have no effect on the inhibition produced by norepinephrine (NE) and NE itself has no effect on the inhibition produced by morphine. LSD (0.1 mcg/ml) can antagonize the inhibitory effects of 5-HT, but can also produce a marked potentiation of the response to morphine. There may be a cross-over point between the pathway that mediates some of the effects of 5-HT and that which mediates the inhibitory effects of morphine. This crossover point might involve ATP, since it has been suggested that some of the inhibitory effects of 5-HT may involve the release of ATP. The effects of ATP and morphine are altered by tolazoline and phosphodesterase inhibitors. - Morphine may act to inhibit responses of the gut to field stimulation by releasing ATP or some of its derivatives, or morphine might act by mimicking the effects of adenosine or ATP. It is suggested that the ATP-cAMP pathway that mediates the effects of purinergic transmission is probably the neuro--chemical pathway that mediates the actions of morphine.
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