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Greengard P. 
“Cyclic nucleotides, phosphorylated proteins and the nervous system”. 
Federation Proc.. 1979;38(8):2208-17.
The role of cyclic nucleotides and phosphorylated proteins in the neuronal effects of neurotransmitters is reviewed. cAMP and cGMP appear to act as mediators or modulators in some of the postsynaptic effects of several classes of neurotransmitters. There appears to be 2 general classes of mechanism by which this process may occur: the 'receptor-ionophoreĠ and the 'receptor-second messenger' model. There is now evidence for 2 types of synaptic transmission involving the receptor second messenger system. The postsynaptic cell of the receptor-second messenger modulatory synapse can be either the presynaptic or the postsynaptic cell of the synapse being modulated. An adenylate cyclase in the nervous tissue activated by low concentrations of neurotransmitter has been demonstrated for dopamine, serotonin, noradrenaline, histamine and octopamine. The representative antagonists for these neurotransmitters, respectively, are chlorpromazine, LSD, propranolol, metiamide and phentolamine and they in general block the activation by the neurotransmitter of the particular adenylate cyclase. ACh (muscarinic, histamine (H), noradrenaline (a) and glutamate cause increases in cGMP in certain target cells. The representative antagonists of the first 3 neurotransmitters are atropine, diphenhydramine and phentolamine. Available evidence suggests that the molecular mechanism by which the cyclic nucleotides carry out the 2nd messenger role in nerve cells involves regulation of the state of phosphorylation of specific neuronal proteins. Several CNS depressants including pentobarbital, chloral hydrate and urethane administered to mice i.p. decrease the state of phosphorylation of Protein I and conversely, the convulsant drugs, pentylenetetrazole and picrotoxin increase the state of phosphorylation of Protein I, in whole brains of mice in vivo Phosphorylated proteins also appear to be involved in mediating certain of the actions of several other classes of regulatory agents, including calcium and the steroid hormones (mineralocorticoids, glucocorticoids, estrogens and androgens).
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