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Paul Greengard

Nerve cells release different transmitters that activate specific receptors located in the cell membrane. Drugs like cocaine and amphetamine enhance the synaptic dopamine levels; other drugs like opiates act directly on receptors. Antipsychotic drugs block dopamine receptors.

Paul Greengard showed that the activation of receptors changes levels
of intracellular messengers like cyclic AMP, which in turn cause a cascade of enzyme reactions. The final result is addition or removal of phosphate groups from target proteins such as ion channels that control the excitability of nerve cells. The phosphate groups change the form and function of the protein.

 

In some nerve cells there is an intermediate stage, with the molecule DARPP-32 serving as a master switch. It orchestrates the degree of phosphorylation in different molecular targets in the cell membrane and cytoplasm.

 

Other targets (e.g. pCREB) regulate protein synthesis by activating genes in the cell nucleus. DARPP-32 is involved in mediating, for instance, the sense of pleasure and is indirectly affected by drugs of abuse.



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