5'-triphosphate (ATP) has long been known to be responsible
for the storage and provision of metabolic energy in biological
organisms. However, in the past few decades an unexpected extra-cellular
function of ATP has emerged. For long, it had been postulated
that ATP is released from nerves and it acts upon target cells
in order to transmit signals across synapses (the space between
nerve cells and target cells), i.e. as a synaptic neurotransmitter.
In mediating this function, ATP joined the ranks of neurotransmitter
molecules such as: the better-known acetylcholine (ACh), noradrenaline
(NA), serotonin (5-HT), dopamine (DA), and gamma-amino butyric
acid (GABA). It was in the late sixties and early seventies,
with the discovery and elucidation of "purinergic" nerves,
that the possible role of ATP as a neurotransmitter was propounded.
Studies on the neurotransmitter function of ATP led to the
discovery of an even more interesting phenomenon. Individual
neurons of the autonomic nervous
were found to contain and release ATP along with a classical neurotransmitter
like ACh and NA, thus giving rise to the concept of "Co-transmission".
Co-transmission has been described as the co-localization and co-release of two
or more neurotransmitters upon nerve stimulation from the same nerve terminals,
to act on the post-synaptic cells to carry out the process of neurotransmission.
The actions of co-transmitters on the post-synaptic cells have been reported
to be either synergistic or antagonistic. Indeed, studies on purinergic co-transmission
in the CNS have given rise to interesting insights on how transmitters might
interact to produce novel patterns of postsynaptic activation, unobtainable by
either transmitter alone.
Research at IIT Bombay
This novel feature of co-transmission by ATP along with other
neurotransmitters alters our concept of the biophysics and
biochemistry of neurotransmission
at these synapses. In the nerve-muscle physiology laboratory of the School
of Biosciences & Bioengineering,
we are investigating various aspects of both these issues, i.e. the involvement
of ATP as a synaptic neurotransmitter and its significance in co-transmission.
any molecule to be classified as a neurotransmitter there are
certain criteria that need to be fulfilled. For example,
for every neurotransmitter,
and storage in the nerve terminals have to be demonstrated. Further,
it should be shown that the proposed neurotransmitter is released
on nerve stimulation. External application of a neurotransmitter should
mimic the response to nerve stimulation, and finally, an effective system
inactivation of the neurotransmitter molecule from the synapse should
be present........ more on next page