Phospholipase angiotensin

Gq Angiotensin Phospholipase C Muscle contraction, blood pressure elevation... 

The same basic biochemical control mechanism causes contraction of the smooth muscle as well as secretion of aldosterone. The binding of angiotensin to its receptor activates a membrane phospholipase-C. It catalyses the hydrolysis of phosphoinositide phosphatidylinositol bis-phosphate to produce the two intracellular messengers, inositol trisphosphate (IP3) and diacylglycerol (DAG). 

The cq receptors are activated not only by catecholamines but also by the hormones vasopressin and angiotensin n. Binding of these hormones to a, receptors induces a complex response that involves rapid hydrolysis of phosphatidylinositol derivatives and release of Ca2+ into die cytoplasm, and of diacylglycerols into the lipid bilayer of the membrane. The response is mediated by another G protein called Gq.27 1 275 When this G protein is activated it induces the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP2), a normal minor component of the lipid bilayer, by phospholipase C (phosphoinositidase C).265,276 281... 

Angiotensin II has a variety of effects. By constricting blood vessels it raises blood pressure, and by stimulating thirst centers in the brain it increases blood volume. Both angiotensins II and III also act on the adrenal gland to promote the synthesis and release of aldosterone. Most of the effects of angiotension II are mediated by 359-residue seven-helix G-protein linked receptors which activate phospholipase C.p q qr Like other steroid hormones aldosterone acts,via mineralocorticoid receptors, to control transcription of a certain set of proteins. The end effect is to increase the transport of Na+ across the renal tubules and back into the blood. Thus, aldosterone acts to decrease the loss of Na+ from the body. It promotes retention of water and raises... 

Arachidonic acid is not present in significant amounts in tissues as the free acid but is stored as a fatty acid at the sn-2 position of phospholipids. Prostaglandin biosynthesis is initiated by the interaction of a stimulus with the cell surface. Depending on the cell type, the stimulus can take the form of a hormone, such as angiotensin II or antidiuretic hormone, or a protease such as thrombin (involved in blood clotting), or both hormone and protease. These agents bind to a specific receptor that activates a phospholipase A2 that specifically releases the arachidonic acid from a phospholipid such as phosphatidylcholine. The release of arachidonic acid by phospholipase A2 is believed to be the rate-limiting step for the biosynthesis of eicosanoids. 

G,i. Gi2, Gi3 Norepinephrine, prostaglandins, opiates, angiotensin, many peptides Adenylate cyclase Phospholipase C Phospholipase A2 K+ channels... 

A number of cardiovascular disease states that eventually result in chronic congestive heart failure are associated with alterations in cardiac performance. Several hormonal factors such as angiotensin II, endothelin, and alterations in signal transduction mechanisms including adenylyl cyclase and phospholipase C (PLC) have been reported to play an important role in the alterations of cardiac performance. 

Fig. 5.2 Early G-protein signaling events at the AT]R. Phospholipases C and D are sequentially activated by heterotrimeric G-protein subunits to produce important second messengers such as IP3 and DAG. See text for details. ATiR, angiotensin II type 1 receptor DAG, diacylglycerol IP3, inositol 1,4,5-trisphosphate PA, phosphatidic acid PC, phosphatidylcholine PIP2, phosphatidylinositol-4,5-bisphosphate PKC, protein kinase C PLC, phospholipase C PLD, phospholipase D.

Haendeler, J., Yin, G., Hojo, Y., et al. 2003. GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor. J Biol Chem 278 49936-49944. 

Marie, J., Maigret, B., Joseph, M. P., et al. 1994. Tyr292 in the seventh transmembrane domain of the AT1A angiotensin II receptor is essential for its coupling to phospholipase C. J Biol Chem 269 20815-20818. 

Rao, G. N., Lassegue, B., Alexander, R. W., et al. 1994. Angiotensin II stimulates phosphorylation of high-molecular-mass cytosolic phospholipase A2 in vascular smooth-muscle cells. Biochem J299(Pt 1) 197—201. 

Ushio-Fukai, M., Griendling, K. K., Akers, M., et al. 1998b. Temporal dispersion of activation of phospholipase C-betal and -gamma isoforms by angiotensin II in vascular smooth muscle cells. Role of alphaq/11, alphal2, and beta gamma G protein subunits. J Biol Chem 273 19772-19777. 

Fig. 6.4 Proposed scheme for ATj-mediated transactivation of the EGF receptor and the subsequent activation of ERK1/2. The interaction of angiotensin II with the ATi receptor stimulates several pathways that result in the transactivation of the EGF receptor. In one pathway, phospholipase C (PLC) is activated, which in turn promotes the production of reactive oxygen species (ROS). ATj receptor activation also elevates [Ca2+]j, contributing to the stimulation of a Ca2+-dependent tyrosine kinase, of which Src and proline-rich tyrosine kinase-2 (Pyk2) are the preferred targets. Both ROS and the Ca2+-dependent tyrosine kinase activate a metalloprotease, presumably ADAM17, which proteolytically activates the EGF ligand. The Ca2+-dependent tyrosine kinase, as well as a Ca2+-independent kinase, also phosphorylate the EGF receptor. The activation of the EGF receptor triggers a cascade leading to the activation of ERK1/2. EGF receptor transactivation also proceeds via a G-protein-independent pathway (see text).

Li F, Malik KU. 2005. Angiotensin Il-induced Akt activation through the epidermal growth factor receptor in vascular smooth muscle cells is mediated by phospholipid metabolites derived by activation of phospholipase D. J Pharmacol Exp Ther 312 1043-1054. 

Protein kinase C (PKC) may play a role in tonic tension. PKC refers to a family of related serine/threonine kinases, five of which are found in smooth muscle. PKC is activated by diacylglycerol, or DAG. DAG (and also IP3) is liberated from membranes by the action of phospholipase C (PLC) on phosphatidylinositol 4,5-bisphosphate, or by the action of phospholipase D (PLD) on phosphatidylcholine. A number of receptor-mediated events are transduced by activation of these lipases. Some agents that elicit tonic contraction (e.g., angiotensin II) activate PLD, thus producing DAG (but not IP3), which activates PKC with no effect on [Ca +]j. There are at least three sites on LC20 that can be phosphorylated by PKC, but it is not known which one, if any, of these is involved in the induction of contraction and latch. 

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