Protein linked

Stmctural defects at the receptor level are determinant for a number of receptor diseases. In nephrogenic diabetes insipidus, where patients void large volumes of dilute urine even in the presence of vasopressin (antidiuretic hormone) (105), the disease is linked to mutations in three discrete regions of the G-protein-linked vasopressin (V2) receptor (106,107). 

Pseudohypoparathyroidism is characterized by end-organ resistance to parathyroid hormone (98,108). This disease takes various forms, including Albright s hereditary osteodystrophy, which has unusual physical features and a generalized resistance to G-protein-linked hormones that function through cAMP as a second messenger. This defect is associated with a deficiency in the levels of the a-subunit of (109). Because this defect may be generalized, such patients also have olfactory dysfunction (110). 

Bacterial or viral proteins linking T-cell receptors and MHC molecules through simultaneous interaction with the constant domains of all MHC class II molecules and of T-cell receptor (3-chains. Hence, superantigens are polyclonal T-cell activators most likely involved in the development of autoimmune diseases. 

Ca may activate phospholipase A2 and cause production of lyso-lipids and fatty acids. In addition, ionic fluxes across the membrane occur, leading to pH changes and membrane depolarization. It is not clear how these other responses are initiated, but there may be direct G-protein links to effector systems such as phospholipase A2 or ionic channels. 

Morris AJ, Malbon CC Physiological regulation of G protein-linked signaling. Physiol Rev 1999 79 1373. 

Not all influences on, or potentials recorded from, a neuron have the same time-course as the EPSP and IPSP, which follow the rapid opening of Na+ and Cl ion charmels directly linked to NT receptors. There are also slowly developing, longer lasting and smaller non-propagated (conditioning) changes in potential most of which appear to have a biochemical intermediary in the form of G-proteins linked to the activation (Gs) or... 

In the spinal cord GABA can also activate the G-protein-linked GABAb receptor, also found pre- and postsynaptically. Baclofen modulation of nociceptive transmission is seen under inflammatory conditions in animals but in humans the drug appears to lack any analgesic effect. 

Birdsall NJ, Cohen F, Lazareno S, Matsui H. Allosteric regulation of G-protein-linked receptors. Biochem Soc Trans 1995 23 108-111. 

One attempt to overcome these disadvantages has been to use multidimensional liquid chromatography (LC) followed directly by tandem mass spectrometry to separate, fragment and identify proteins (Link et al., 1999). In this process, a denatured and reduced protein mixture is digested with a protease to create a collection of peptides (Fig. 2.6). The peptide mixture is applied to a cation exchange column and a fraction of these peptides are eluted based on charge onto a reverse-phase column. The... 

If ft receptors couple to K+ channels and adenylyl cyclase via different G proteins, it is possible that chronic morphine treatment uncouples the receptor from those G proteins linked to the K+ channel and not those coupling fi receptors to adenylyl cyclase. Such a hypothesis would require that G proteins couple to different intracellular domains of the fi receptor so that interaction of G proteins with some domains could be blocked by post-translational events, such as phosphorylation, whereas binding of G proteins to other fi receptor domains would not be affected. 

The finding that extracellular loop 2 of the k receptor is a ligand binding domain is not unique among G protein-linked receptors. Recent mutagenesis stud-... 

Ma GH, Miller R, Kuznestov A et al. Kappa-opioid receptor activates an inwardly rectifying K+ channel by a G protein-linked mechanism coexpression in Xenopus oocytes. Mol Pharmacol 1995 47 1035-1040. 

DeMar Jr. J.C., Disher, R.M., and Wensel, T.G. (1992) HPLC analysis of protein-linked fatty acids using fluorescence detection of 4-(diazomethyl)-7-diethylaminocoumarin derivatives Abstract 465. Biophys. J. 61(A81). 

FIGURE 14-6 Main signaling pathways for histamine receptors. Histamine can couple to a variety of G-protein-linked signal transduction pathways via its four different receptors. The Hj receptor activates the phosphatidylinositol turnover via Gq/11 proteins. The other receptors either positively (H2 receptor) or negatively (H3 and H4 receptor) regulate adenylyl cyclase activity via Gs and GUo protein activation respectively. Several additional signaling pathways have been described, which are not shown. Abbreviations PfP2, phosphatidylinositol 4,5-bisphosphate PIC, phospholipase C AC, adenylyl cyclase ATP, adenosine triphosphate cAMP, cyclic AMP PKC, protein kinase C PICA, protein kinase A. 

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