Messenger®, production

Figure 10. The G-protein cascades in smooth muscle catalyze the exchange GDP for GTP on G-protein. Following the binding of GTP, the trimeric G-protein splits into an a-GTP part and a P-y part. The a-GTP part ordinarily then combines with its specific apoenzyme to constitute the active enzyme. For the activation of the contractile activation path, the enzyme is phospholipase C and the second messenger products are IP3 and DAG. The IP3 in the myoplasm binds to Ca channels in the SR membrane, opening them. Other second messengers include the inhibitors of contractile activity, cGMP and cAMP.

An additional action of Li" is interruption of the phosphatidylinositide cycle through an inhibitory action on inositol phosphate metabolism. By this mechanism, depletion of membrane inositol and the phosphoinosi-tide-derived second-messenger products diacylglycerol and inositol triphosphate ultimately reduces signaling through receptor systems dependent on the formation of these products. It is presently unclear to what extent inhibition of inositol phosphate metabolism contributes to the therapeutic properties of Li+ in bipolar patients. 

Roth BL, Shoham M, Choudhary MS, Khan N. Identification of conserved aromatic residues essential for agonist binding and second messenger production at 5-hydroxytryptamine2A receptors. Mol Pharmacol 1997 52 259-266. 

Frederick JP, Mattiske D, Wofford JA, Megosh LC, Drake LY, Chiou ST, Hogan BL, York JD. An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse embryogenesis and second messenger production. Proc. Natl. Acad. Sci. U.S.A. 2005 102 8454-8459. 

It is now clear that there are nine PG distinct receptors each encoded by a different gene (Fig. 2 [11]. For example, in the case of PGEj, four different prostaglandin E (EP) receptors have been identified and designated as EPl, EP2, EP3, and EP4 receptors. Based on studies with selective agonists for each of the EP receptors and their effects on second messenger production, it appears that EPl is coupled to Ca mobilization, EP2 and EP4 are coupled via G to the stimulation of adenylate cyclase, and EP3 receptors are coupled via Gj to the inhibition of adenylate cyclase. 

GPCR Gj/ coupled Autoreceptor function inhibits transmitter release GPCR G, G. coupled GPCR g ,jj coupled modulatory regulates ion channels, second messenger production, and protein phosphorylation GPCR G coupled GPCR G, jj coupled... 

GPCR G, jj coupled modulatory regulates ion channels, second messenger production, and protein phosphorylation... 

These data show that in RBL cells 5-HT transport could be regulated differentially by different receptor mediated second messenger production. According to amino acid sequence analysis the 5-HT transporters in the RBL cells and in the brain cells are identical. 

In the foUowing, we wiU describe assays to assess several outcomes of chemokine receptor signaling, starting with G protein activation, secondary messenger production, and P-arrestin recruitment, continuing with further downstream signaUng (e.g., ERK phosphorylation), and finaUy assessing the chemotactic response. 

Spielman, A.I., H. Nagai, G. Sunavala, M. Dasso, H. Breer, I. Boekhoff, T. Huque, G. Whithey, J.G. Brand, Rapid kinetics of second messenger production in bitter taste, Amer. J. Cell Physiol., 1996(270) p. 926. 

Somatostatin is thought to act through an inhibitory G protein to interfere with receptor-mediated second messenger production, explaining the inhibition of histamine stimulation. In the case of EGF, the inhibition appears to occur at a site beyond the Hz receptor, because EGF also inhibits dibutyryl cAMP stimulation of acid formation. The PG EP3 receptor has been shown to reduce cAMP levels, and, presumably, bonding to this receptor by relatively nonselective PGEz compounds accounts for their inhibition of acid secretion. 

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