Mediated intracellular signaling pathways

Three phases of receptor-mediated signaling can be identified 178 Four distinct molecular mechanisms that link agonist occupancy of cell-surface receptors to functional responses have been identified 178 Cross-talk can occur between intracellular signaling pathways 179 Signaling molecules can activate gene transcription 181 Nitric oxide acts as an intercellular signaling molecule in the central nervous system 181... 

Fig. 1. Major chemokine and IL-3/IL-5/GM-CSF-mediated intracellular signal transduction pathways in granulocytes.

Iwai-Kanai, E., and Hasegawa, K. 2004. Intracellular signaling pathways for norepinephrine- and endothelin-1-mediated regulation of myocardial cell apoptosis. Mol. Cell. Biochem. 259 163-168. 

Modulatory effects may be postsynaptically mediated by interactions within the spiny projection neurons, or involve presynaptic regulation of neurotransmitter release from corticostriatal terminals. Postsynaptic effects may be mediated by direct actions of intracellular signaling pathways (cAMP, calcineurin) on receptor status (phosphorylation/ dephosphorylation of receptor proteins), and actions on voltage-dependent channels, which may amplify or attenuate the electrical response of the cell to synaptic currents. 

An example of agonist-specific coupling is shown in Figure 8.3. The receptor in question is the -adrenergic receptor. This receptor triggers at least two different intracellular signaling pathways Arachidonic acid is released by phospholipase A2, and inositoltriphosphate (IP3) is released by phospholipase C. These two effects are mediated by two different G proteins that couple to the same receptor. If we compare the two parameters, the three compounds norepinephrine and meta- and para-octopamine yield substantially different potencies and efficacies. If we hadn t been told otherwise, we would interpret this observation as evidence of two different receptors. In a sense, of course, different GPCR-G protein complexes are different receptors. 

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