Calcium messenger system

Most extracellular messengers that cause a rise in cytosolic Ca + concentration also increase the turnover 

Gq protein-coupled phosphatidylinositol-Ca pathway. The binding of a hormone at a specific receptor site results in the activation of G-protein which, in turn, activates phospholipase C via Gga-OTP-protein. The action of phospholipase C on phosphatidylinositol 4,5-bisphosphate (PIP2) yields inositol trisphosphate (IP3) and diacylglycerol (DAG) which, along with phosphatidylserine (PS), activates protein kinase C. IP3 binds to receptors on SER, releasing Ca which, in turn, activates another set of protein kinases. -I-, Activation. 

Structure of phosphatidylinositol 4,5-bisphosphate. Hydrolysis at the dotted line is catalyzed by phospholipase C and releases diacylglycerol and inositol 1,4,5-trisphosphate, which are the intracellular second messengers. 

In several types of cells, stimulation of plasma membrane receptors coupled to phosphoinositide turnover not only triggers a rapid mobilization of intracellular Ca + as discussed above, but also a prolonged mobilization. 

Following these early events initiated by binding of a calcium-mediated hormone to its receptor, a transient rise in cytosolic calcium concentration and a more prolonged increase in DAG concentration occur. There is also a prolonged four- to fivefold increase in Ca flux across the 

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Unfortunately, at the present time the physiological function of the majority of calcium binding proteins is unknown, and before the complexity of the calcium messenger system can be completely elucidated, the function of these proteins must be clarified. Accordingly, the purpose of the review is to briefly document the various cellular calcium binding proteins and where possible discuss the role of these proteins in the signal transduction process. Since our knowledge of the role of cal-... 

On the basis of results obtained from studies in adrenal glomerulosa, vascular smooth muscle and hepatic cells, it is evident that the major effects of All on cell function are mediated via an activation of the calcium messenger system. Furthermore, the data, although far from complete, provide convincing evidence that a temporal and spatial pattern of events underlies hormonal action. 

The cellular mechanism of lead nephrotoxicity appears to be due to an alteration of calcium homeostasis. Lead (Pb ) competes with calcium (Ca " ") for transport, binding to calmodulin and at other cell calcium regulatory sites. Lead can accumulate in mitochondria using the calcium transporter and disrupt respiration. Interactions of lead with calmodulin can result in a disruption of the calcium messenger system to adversely affect normal cell function. The nuclear inclusion bodies may also alter the cellular function of DNA, although this interaction has not been fully elucidated. 

There are numerous second messenger systems such as those utilizing cyclic AMP and cyclic GMP, calcium and calmodulin, phosphoinosiddes, and diacylglerol with accompanying modulatory mechanisms. Each receptor is coupled to these in a variety of ways in different cell types. Therefore, it can be seen that it is impractical to attempt to quantitatively define each stimulus-response mechanism for each receptor system. Fortunately, this is not an... 

Screening. See High-throughput screening Second messenger systems calcium ion, 83 description of, 24 production of, 25f Series hyperbolae, 38 Serotonin, 150, 151 f Seven transmembrane receptors, 3-4 Shennong Herbal, 147 Short interfering RNA duplex molecules, 184... 

Dubovsky SL, Murphy J, Christiano J, et al The calcium second messenger system in bipolar disorders data supporting new research directions. J Neuropsychiatry Chn Neurosci 4 3-14, 1992b... 

Oxytocin acts through G protein-coupled receptors and the phosphoinositide-calcium second-messenger system to contract uterine smooth muscle. Oxytocin also stimulates the release of prostaglandins and leukotrienes that augment uterine contraction. Oxytocin in small doses increases both the frequency and the force of uterine contractions. At higher doses, it produces sustained contraction. 

Another second messenger system, the inositol triphosphate-diacylglycerol system, can also be activated by cholinergic or adrenergic receptors. It involves calcium movement and will be discussed when and if time permits. 

Other actions of some anticonvulsants include inhibition of the enzyme carbonic anhydrase, negative modulation of calcium channel activity, and actions on second messenger systems, including inhibition of phosphokinase C. Beyond the second messenger, there is the possibility that second messenger systems may be affected, analogously to what is hypothesized for lithium. 

A lithium chloride solution caused changes in gravicur-vature, statocyte ultrastructure, and calcium balance in pea root, believed to be due to effects of lithium on the phosphoinositide second messenger system (678). The implications with regard to human parathyroid function are obscure. 

The second messenger molecules Ca2+ and cyclic AMP (cAMP) provide major routes for controlling cellular functions. In many instances, calcium (Ca2+) achieves its intracellular effects by binding to the receptor protein calmodulin. Calmodulin has the ability to associate with and modulate different proteins in a Ca2+-dependent and reversible manner. Calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE, EC 3.1.4.17) is one of the key enzymes involved in the complex interactions that occur between the cyclic-nucleotide and Ca2+ second messenger systems (see Figure 13.2). CaMPDE exists in different isozymic forms, which exhibit distinct molecular and catalytic properties. The differential expression and regulation of individual phosphodiesterase (PDE) isoenzymes in different tissues relates to their function in the body. 

The mechanism of action for aluminum toxicity is not known, but the element is known to compete in biological systems with cations, especially magnesium (MacDonald and Martin 1988) despite an oxidation state difference, and to bind to transferrin and citrate in the blood stream (Gannot 1986). It may also affect second messenger systems and calcium availability (Birchall and Chappell 1988), and irreversibly bind to cell nucleus components (Crapper-McLachlan 1989 Dryssen et al. 1987). Aluminum has also been shown to inhibit neuronal microtubule formation. However, much more work is needed before a mechanism can be proposed. 

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