Presynaptic autoreceptors regulating transmitter release

The discovery that the cytoplasmic membrane of presynaptic nerve terminals possess receptors that modulates release of neurotransmitters was made 35 years ago. This new concept represents a clear departure from the traditional view that neuronal communication was unidirectional, i.e. from the nerve terminal to the postsynaptic receptor, because the transfer of information via presynaptic receptors occurs in the opposite direction: from the synaptic cleft to the nerve terminals which release the neurotransmitter. Presynaptic release-modulating autoreceptors and heteroreceptors represent suitable targets for pharmacological intervention by exogenous compounds acting as agonists, partial agonists or antagonists. Such compounds may be of therapeutic value by influencing transmitter release presynaptically, and having fewer side effects than the well-established approach of using agonists or antagonist drugs to stimulate or block postsynaptic receptors.