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Vol. 290, Issue 1, 241-246, July 1999
Department of Pharmacology, University of Nevada School of
Medicine, Reno, Nevada
Recent reports have suggested that sympathetic nerves may store
separately and release independently the cotransmitters ATP and
norepinephrine (NE). It is conceivable therefore that the quantity of
each neurotransmitter that is released from the nerves is not fixed but
rather may vary, possibly with the frequency of stimulation. To test
this hypothesis we studied the concomitant release at various
frequencies and cooperative postjunctional actions of ATP and NE during
the first 10 s of electrical field stimulation of the guinea pig
vas deferens. We found that at lower frequencies (8 Hz), prejunctional
inhibition of the release of NE, which occurs via
2-adrenoceptors, modulates the ultimate composition of
the cocktail of cotransmitters by limiting the amount of NE that is
coreleased with ATP. As the frequency of stimulation increases (above 8 Hz), the autoinhibition of the release of NE is overridden and the
amount of NE relative to ATP increases. The smooth muscle of the guinea
pig vas deferens reacts to changes in composition of the sympathetic
neurochemical messages by increasing the amplitude of its contractions
due to the enhancement by NE of the contractile responses triggered by
ATP. This evidence suggests that the prejunctional
2-adrenoceptor may function as a sensor that "reads"
the frequency of action potentials produced during a burst of neuronal
activity and converts that information into discrete neurochemical
messages with varying proportions of cotransmitters. The mechanism for
decoding the informational content of these messages is based on the
cooperative postjunctional interactions of the participating cotransmitters.
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