Measurement of the in vitro release of endogenous monoamine neurotransmitters as a means of identification of prejunctional receptors.

In contrast to in vivo release methods, in vitro release techniques utilising brain slices or synaptosomes affords a simple and reproducible means of measuring both receptor affinity and efficacy of drugs acting at prejunctional receptors in the CNS. Most studies have used brain tissue loaded with radiolabelled neurotransmitter or its precursor via the high affinity uptake system for these substances which are present on nerve terminals. Depolarisation evoked release induced by either high K+ or electrical field stimulation increases the release of radioactivity and this overflow can be readily measured by liquid scintillation counting. Recent studies have started to emphasise the measurement of the release of endogenous neurotransmitters from brain tissue using similar depolarisation stimuli. Examples include the release of dopamine, noradrenaline, adrenaline and 5-HT and their control by presynaptic receptors. Most of these studies have used HPLC with ECD detection as a means of separating and analysing for the transmitter of interest. The relative strengths and weaknesses of the measurement of radiolabelled or endogenous neurotransmitter release in vitro as a means of identifying presynaptic receptors is discussed.