Intraneuronal Signaling Pathways

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document in English

biology

research papers

published 26/11/2007

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Prior to delineating the organization of specific intraneuronal signaling pathways, it is important to consider, in general terms, their role in helping neurons interpret and respond to the barrage of afferent stimulation impinging on them continuously. From an evolutionary perspective, second messenger systems predate neurotransmitters and neurotrophins, examples of first messengers detected by cell surface receptors. Before the advent of neurotransmitters, prokaryotic organisms relied on cyclic adenosine monophosphate (cAMP) and other intracellular signaling pathways to coordinate diverse responses located in disparate parts of these unicellular organisms to changes in ambient nutrients or conditions. Neurotransmitters and neurotrophins have evolved subsequently to take advantage of these internal signaling pathways that have undergone a parallel growth process.

Intraneuronal signaling pathways do more than merely enlarge the sphere of influence of afferent stimuli beyond the local environment of the cell surface receptor.
Although the overwhelming majority of psychiatric drugs target extracellular receptors or uptake sites, the explosion of information on intraneuronal signaling pathways suggests that these may represent suitable drug targets.
Psychiatrists have long been taught that a true understanding of normal and abnormal behavior requires an appreciation of the interplay of forces lurking beneath the surface.
Neurotransmitter receptors may couple to adenylate cyclase via different classes of G proteins, referred to as Gs or Gi, depending on whether they stimulate or inhibit cyclic AMP formation.
Cyclic GMP Besides cyclic AMP, another cyclic nucleotide, cyclic guanosine monophosphate (GMP) has been identified as a second messenger regulated by neurotransmitter receptor stimulation.
Because the effects of cAMP are mediated to a large extent via activation of a kinase, it was generally assumed that each of these second messengers acted in a similar fashion.
However, this view has been challenged recently in light of animal studies demonstrating that inositol levels in brain are unaffected by lithium concentrations within its therapeutic range.
These alternate arrangements emphasize the notion that intracellular signaling cascades have evolved in ways that heighten their versatility, with each of the components having multiple signaling capacities.
Another family of tyrosine kinases has been identified that differs from the receptor tyrosine kinases in that it contains only the cytoplasmic domain.
Cross-Talk Among Signaling Pathways The organization of intraneuronal signaling pathways allows for a high degree of interaction or cross-talk among pathways