Tyrosine intracellular second messengers

There are several mechanisms whereby antidepressants can modify intracellular events that occur proximal to the posts)maptic receptor sites. Most attention has been paid to the actions of antidepressants on those pathways that are controlled by receptor-coupled second messengers (such as cyclic AMP, inositol triphosphate, nitric oxide and calcium binding). However, it is also possible that chronic antidepressant treatment may affect those pathways that involve receptor interactions with protein tyrosine kinases, by increasing specific growth factor synthesis or by regulating the activity of proinflammatory cytokines. These pathways are particularly important because they control many aspects of neuronal function that ultimately underlie the ability of the brain to adapt and respond to pharmacological and environmental stimuli. One mechanism whereby antidepressants could increase the s)mthesis of trophic factors is... 

Growth hormones, important in diabetes and cancer, activate a receptor with an intrinsic intracellular tyrosine protein kinase activity that passes on the signal by phosphorylating other proteins, often kinases themselves. To date, no specific second messengers have been associated with these systems. The amplification occurs by the turn-on of the receptor-associated protein kinase activity that can phosphorylate many proteins. 

The insulin receptor represents a somewhat different class of cell-surface receptors that contain intrinsic hormone-activated tyrosine kinase activity and do not otherwise involve a second messenger. " The insulin receptor is the prototype of this type of receptor and consists of two a and two p subunits joined by disulfide bridges. The extracellular, hormone-binding domains are the a subunits, and the P subunits are intracellular. They contain an ATP binding site... 

The H2 receptor is a 359-amino-acid protein in humans. It has some features similar to the Hi protein (e.g., N-terminal glycosylation sites) and phosphorylation sites in the C-terminal. An aspartic acid residue in the third transmembrane loop appears to be critical to agonist and antagonist binding, and threonine/aspartate and tyrosine/aspartate couples in the fifth transmembrane domain appear to be important for interaction of the imidazole part of the histamine molecule. It is positively coupled via Gas to activate adenylyl cyclase for synthesis of cyclic adenosine monophosphate (cAMP) as a second messenger. In some systems, it is coupled through Gq proteins to stimulate phospholipase C. It appears in some cells that other processes, such as breakdown of phosphoinositides, control of intracellular calcium ion levels, and phospholipase A2 activity, can be regulated by other cAMP-independent pathways. 

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