Corelease of Noradrenaline and Adenosine Triphosphate from Sympathetic Neurones

Abstract

Publisher Summary In many sympathetically innervated tissues, both noradrenaline and ATP are involved in the postjunctional responses to nerve action potentials. In agreement with this cotransmitter role of ATP, electrical stimulation of axons and depolarization by high K + concentrations elicit the release of ATP from sympathetically innervated tissues. This overflow constitutes one basic piece of evidence for the view that ATP is a transmitter in the postganglionic sympathetic nervous system. To overcome the problem of data interpretatioin and function of sympathetic nerves, the postjunctional responses to released noradrenaline and ATP were blocked in some studies to abolish the nonneural release of ATP. This chapter shows the overflow of [3H]-noradrenaline and ATP from these cultured neurones induced by 100 electrical pulses applied at 10 Hz. The evoked overflow of ATP was abolished by tetrodotoxin as well as by omission of calcium from the medium, indicating that it was because of an action potential-evoked, Ca 2+ -dependent exocytosis. Postganglionic sympathetic axons also possess receptors for ATP itself. ATP and ATP analogues inhibit the release of noradrenaline by activation of presynaptic P2-purinoceptors in sympathetically innervated tissues, such as the mouse vas deferens, the rat iris, the rat heart atrium, and the rat tail artery. The chapter highlights three examples for differential modulation of cotransmitter release. The mechanisms of this differential control of cotransmitter release are yet unknown. There remain at least two possibilities. First, in the same axons there may be different populations of vesicles with a different cotransmitter mixture, and the probability of exocytosis from noradrenaline-rich and ATP-rich vesicles may be controlled through different mechanisms; second, there may be different populations of axons differing in their vesicular noradrenaline/ATP ratio as well as in their control of the probability of exocytosis.