Paul Greengard

Picture of Paul Greengard

Date of Birth: 11/12/1925

Age: 90

Place of birth: New York

Citizenship: United States


G. awarded in Physiology or Medicine Nobel Prize for his discovery of the mechanism of action of dopamine and other neurotransmitters at synaptic transmission.

Acting on a cell membrane receptor, a neurotransmitter triggers phosphorylation reactions special "key" proteins. Modified proteins, in turn, form ion channels in the membrane, and through which signals are transmitted. Various ion channels of the cell determine its response to the impact.

In the late 60s it was already known that dopamine, norepinephrine and serotonin are neurotransmitters, but their mechanism of action remains unclear. By the early 70s found that dopamine, norepinephrine and serotonin - mediators in the central nervous system, which have an unusual effect on target cells. In contrast to the fast advancing in milliseconds, the classical effects of amino acid neurotransmitters and acetylcholine, catecholamine action often develops hundreds of milliseconds or seconds and can last even for hours. Such a method of transmitting signals between neurons called "slow synaptic transmission."

In 1979, John Eccles in collaboration with two Canadian biochemists, spouses McGuire, published an article in which he proposed to call the effects of classical fast ionotropic mediators, meaning that they act on ion channels in the synaptic membrane, and the effects of the slow - metabotropic , suggesting that they require involvement of metabolic processes in the postsynaptic neuron. As these authors wrote in 1978, the full story of catecholamines can not be told, because the most important discoveries - deciphering their effects on the postsynaptic cell - has not yet been made.

The veil of uncertainty over this issue, he opened showed that slow synaptic transmission through metabotropic receptors causes a chemical reaction, the phosphorylation inside nerve cells, ie, attaching phosphate groups to proteins with a subsequent change of form and function of these proteins. G. and coworkers found that the binding of dopamine receptors on the cell membrane enhances the cell contents of the "second messenger" - cyclic adenosine monophosphate (cAMP). This activates the enzyme protein kinase A, which is able to phosphorylate many proteins in the nerve cell. Among the proteins are phosphorylated, in particular membrane proteins of various ion channels that control excitability of nerve cells and provide the generation and transmission of nerve impulses neuron. Therefore, dopamine, and other neurotransmitters acting through metabotropic receptors capable of modulating the excitability via the mechanism of nerve cells and their response to mediators acting through ionotropic receptors.

G. found that stimulation of the dopamine receptors of the cell membrane is responsible for receipt of the second mediator - cAMP - in a cage. It activates protein kinase A which is able to attach phosphate molecules to other proteins in the neuron. He found that the process of slow synaptic transmission is associated with the chemical reaction of protein phosphorylation. First neurotransmitter affects a receptor located on the cell surface, that is the trigger of the cascade of reactions that result in the "core protein" neuron regulate various functions. By joining a phosphate group (phosphorylation) or remove it (dephosphorylation) change the shape and function of the protein. These mechanisms of action neurotransmitters can transmit a signal from one neuron to another. G. Opening helped to better understand the mechanism of action of many drugs affecting protein phosphorylation in neurons.

Later G. showed that in brain cells occur more complex processes. Neurotransmitters like dopamine, acting through metabotropic receptors, may cause not only the phosphorylation and dephosphorylation of proteins. However, many of them complex effects mediated intracellular effects on the regulatory protein DARPP-32, which in turn affects the function of many other proteins in the cell. These works G. also allowed to understand the effects of some drugs antipsihotropnyh which, as it turned out, specifically affect the phosphorylation of proteins in different nerve cells.

Thus, investigations have uncovered window into a new world of intracellular effects of mediators, is slow synaptic transmission. They have demonstrated that, in addition to the classic effects are realized through the ionotropic receptors and immediate change in the electrical potential of the membrane, many neurotransmitters (catecholamines, serotonin and certain neuropeptides) have an impact on the biochemical processes in the cytoplasm of neurons. It is these metabotropic effects and an unusually slow due to the action of neurotransmitters, and their long-term, a modulating effect on the function of nerve cells. Therefore, these neurotransmitters are involved are often not in the transmission of fast signals for perception, movement, speech, and in the orchestration of complex conditions of the nervous system - the emotions, attitudes, motivations. An illustration of this thesis is the recent article by his employees in

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