发信人: yanan (花自飘零水自流), 信区: Biology
标 题: Paul GreenGard_ Pi regulation in neural tansmissi
发信站: The unknown SPACE (Mon Oct 9 15:07:56 2000), 站内信件

PAUL GREENGARD

Slow synaptic transmission
Towards the end of the 1960's it was known that dopamine, noradrenaline and serotonin were transmitters in the central nervous system but knowledge about their mechanism of action was lacking. Paul Greengard receives the Nobel Prize for his discoveries
of how they exert their effects at the synapse.
Transmitters such as dopamine, noradrenaline, serotonin and certain neuropeptides transmit their signals by what is referred to as slow synaptic transmission. The resulting change in the function of the nerve cell may last from seconds to hours. This
type of signal transmission is responsible for a number of basal functions in the nervous system and is of importance for e.g. alertness and mood. Slow synaptic transmission can also control fast synaptic transmission, which in turn enables e.g.
speech, movements and sensory perception.

Phosphorylation of proteins changes the function of nerve cells
Paul Greengard showed that slow synaptic transmission involves a chemical reaction called protein phosphorylation. It means that phosphate groups are coupled to a protein in such a way that the form and function of the protein is altered. Paul
Greengard showed that when dopamine stimulates a receptor in the cell membrane this causes an elevation of a second messenger, cyclic AMP, in the cell. It activates a Protein Kinase A, which is able to add phosphate molecules to other proteins in the
nerve cell.
The protein phosphorylation affects a series of proteins with different functions in the nerve cell. One important group of such proteins form ion channels in the membrane of the cell. They control the excitability of the nerve cell and make it
possible for the nerve cell to send electrical impulses along its axons and terminals. Each nerve cell has different ion channels, which determine the reaction of the cell. When a particular type of ion channel is phosphorylated the function of the
nerve cell may be altered by, for example, a change in its excitability.

DARPP-32 - a central regulatory protein
Paul Greengard has subsequently shown that even more complicated reactions occur in particular nerve cells. The effects of the transmitters are elicited by a cascade of phosphorylations and dephosphorylations (that is, phosphate molecules are added or
removed from the proteins). Dopamine and several other transmitters can influence a regulatory protein, DARPP-32, which indirectly changes the function of a large number of other proteins. The DARPP-32 protein is like a conductor directing a series of
other molecules. When DARPP-32 is activated it affects several ion channels altering the function of particular fast synapses.
Paul Greengard's discoveries concerning protein phosphorylation have increased our understanding of the mechanism of action of several drugs, which specifically affects the phosphorylation of proteins in different nerve cells.

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