Receptors secondary messengers

G-Protein coupled receptors (GPCR) represent the start element in secondary messenger producing systems. They comprise a family of over 1000 structurally-related members. These membrane proteins are also called serpentine or seven-helix receptors due to their seven transmembrane domains with an a-helical conformation. Receptors belonging to this class respond to a variety of hormones and neurotransmitters, and they detect odorant molecules or light [3,4]. 

When the receptor interacts with its associated G protein, the conformation of the guanine-nucleotide-binding site is altered. The subunits then dissociate, and a phosphatidylinositol-specific phospholipase C (PI-PLC) is activated [5]. The subsequent hydrolysis of phosphatidylinositol bisphosphate then produces inositol triphosphate (IP3) and diacylglycerol (DAG), which are known to be secondary messengers. For example, the water soluble IP3 is released into the cell where its ultimate targets are the calcium storage organelles from which Ca2+ is released [3]. The presence of DAG in cells is known to activate the cellular enzyme protein kinase C (PKC) [6, 7], which phosphorylates a number of cellular... 

Fig. 2. Activation of an intracellular PLC by an extracellular signal (primary messenger) transduced across the membrane via a receptor and G-protein. The products DAG and IP3 that are produced by the PLC catalyzed hydrolysis of phospholipids are secondary messengers...

Figure 2.4. Relationship between the postsynaptic receptor and the secondary messenger system. GTP=guanosine triphosphate GDP=guanosine diphosphate ATP=adenosine triphosphate AMP=adenosine monophosphate.

At the postsynaptic level, lithium has been shown to reduce the function of beta adrenoceptors, presumably by affecting the coupling between the receptor and the secondary messenger system. This effect only becomes apparent following chronic treatment, which may help to explain the delay of several days, or even weeks, before an optimal beneficial effect is observed. All antidepressants are known to reduce the functional activity of postsynaptic beta receptors, which may explain why lithium has both an antimanic and an antidepressant effect in patients with manic-depression. 

The most common secondary messengers in signal transduction pathways, formed from the primary interaction, are calcium ions (Ca ). The receptor-hormone complex induces changes in the cell s metabolism, usualfy by affecting transcription or translatioiL... 

Cyclic AMP (adenosine 3, 5 -cyclic monophosphate) is anotter secondary messenger that acts as an intracellular mediator for many different hormones, communicating the signal through the cyclic AMP-dependent protein kinase. This, in turn, phosphorylates other proteins at ine and threonine residues. Certain cell-surfece receptors act by increasing the concentration of intracellular cyclic AMP. A long-duration sudden increase of intracellular cyclic AMP takes place with cholera toxins in intestinal epithelial cells. Other cell-surfece receptors play the opposite role of decreasing the concentration of cyclic AMP. 

Prostaglandins (PG s) are naturally occurring intercellular messengers. In fact, many of the actions of anabolic substances fail to exert their protein synthesis actions without them. It is a clinical fact that there is a parallel between the rise of some levels of PG s and the degradation of catabolism. So they may in part be the relay between receptor-sites and translation to specific responses, or secondary messengers. 

Adenylate cyclase The intracellular enzyme associated with some types of receptor that on activation produces the secondary messenger cyclic adenosine monophosphate (cyclic AMP). 

Supporting cells within the brain that act as a physical and metabolic buffer around nerve cells. Family of proteins within neurons that link receptors to ion channels or secondary messengers. 

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