Erowid References Database
“Cyclic Nucleotides and Phosphorylated Proteins as Targets for Drug Action.”.
Acta Pharm. Suecica. 1977;14(Suppl):36-37.
The role of cAMP and protein phosphorylation in the medication of synaptic transmission is discussed. Regulation by cAMP of specific protein phosphorylations appears to regulate the rate of biosynthesis of neurotransmitters in presynaptic nerve terminals to regulate microtubular function in nervous tissue and to mediate the postsynaptic effects of some neurotransmitters. Experiments with mammalian superior cervical ganglion have shown that cAMP (which mediates dopaminergic transmission) and cGMP (which mediates muscarinic cholinergic transmission) together modulate nicotirlic cholinerglc transmission through the ganglion Several neurotransmitter-sensitive adenylate cyclases have been found including noradrenaline - dopamine- and histamine-sensitive adenylate cyclases in mammalian brain and dopamine - octoFamine- and serotonin-sensitive adenylate cyclases in invertebrate nervous tissue. It has been shown that the properties of the neurotransmitter sensitive enzyme correlate with the properties of the neurotransmitter receptor Fluphenazine competitively inhibits (KI = 8 x 10'M) the activation by dopamine of dopamine-sensitive adenylate cyclase in mammalian brain while LSD competitively inhibits (KI = 5 x 10 -9 M) the activation by serotonin of serotonin-sensitive adenylatecyclase in invertebrate nervous tissue. These neurotransmitters and related drugs appear. through effects on specific cyclases to affect the phosphorylation of key proteins and hence modify neuronal function. Results of recent studies indicate that phosphorylated proteins act as general physiological effecters for many classes of regulatory substances in addition to cAMP and include cGMP, steroid hormones. insulin and calcium and drugs which mimic or antagonize the effects of these agents.
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