Second messengers calcium ion

The a.1 receptors are excitatory in their action, while the a2 receptors are inhibitory, these activities being related to the different types of second messengers or ion channels to which they are linked. Thus, a2 receptors hyperpolarize presynaptic membranes by opening potassium ion channels, and thereby reduce noradrenaline release. Conversely, stimulation of ai receptors increases intracellular calcium via the phosphatidyl inositol cycle which causes the release of calcium from its intracellular stores protein kinase C activity is increased as a result of the free calcium, which then brings about further changes in the membrane activity. 

Another major second messenger in cells is calcium ion. Virtually any mammalian cell line can be used to measure transient calcium currents in fluorescence assays when cells are preloaded with an indicator dye that allows monitoring of changes in cytosolic calcium concentration. These responses can be observed in real time, but a characteristic of these responses is that they are transient. This may lead to problems with hemi-equilibria in antagonist studies whereby the maximal responses to agonists may be depressed in the presence of antagonists. These effects are discussed more fully in Chapter 6. 

Second messenger, these are molecules produced by cellular effectors that go on to activate other biochemical processes in the cell. Some examples of second messengers are cyclic AMP, inositol triphosphate, arachidonic acid, and calcium ion (see Chapter 2.2). 

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... 

Plasma membrane channels. The most common mechanism for the movement of into smooth muscle cells Ifom the extracellular space is the electrodiffusion of Ca " ions through highly selective channels. This movement can be significant in two quite different ways. First, Ca ions carry two positive charges and, in fact, most of the inward charge movement across the plasma membrane of smooth muscle myocytes is carried by Ca. Most smooth muscle action potentials are known to be Ca " action potentials. And second, the concentration of intracellular free calcium, the second messenger, is increased by inward calcium movement. 

There are many examples of phosphorylation/dephosphorylation control of enzymes found in carbohydrate, fat and amino acid metabolism and most are ultimately under the control of a hormone induced second messenger usually, cytosolic cyclic AMP (cAMP). PDH is one of the relatively few mitochondrial enzymes to show covalent modification control, but PDH kinase and PDH phosphatase are controlled primarily by allosteric effects of NADH, acetyl-CoA and calcium ions rather than cAMP (see Table 6.6). 

Recently there has been much interest in the possible role of the family of protein kinases which translate information from the second messenger to the membrane proteins. Many of these kinases are controlled by free calcium ions within the cell. It is now established that some serotonin (5-HT) receptors, for example, are linked via G proteins to the phosphatidyl inositol pathway which, by mobilizing membrane-bound diacylglycerol and free calcium ions, can activate a specific protein kinase C. This enzyme affects the concentration of calmodulin, a calcium sequestering protein that plays a key role in many intracellular processes. 

In addition to its role as a bone component, calcium functions as a signaling substance. Ca "" ions act as second messengers in signal transduction pathways (see p. 386), they trigger exocytosis (see p. 228) and muscle contraction (see p. 334), and they are indispensable as cofactors in blood coagulation (see p. 290). Many enzymes also require Ca "" for their activity. The intracellular and extracellular concentrations of Ca "" are strictly regulated in order to make these functions possible (see B, C, and p.388). 

The biosynthesis of peptide hormones and proteohormones, as well as their secretion, is controlled by higher-order regulatory systems (see p. 372). Calcium ions are among the substances involved in this regulation as second messengers an increase in calcium ions stimulates synthesis and secretion. 

Figure 14-3. Signaling through protein kinase C (PKC). Activated phospholipase C cleaves the inositol phospholipid PIP2 to form both soluble (IP3) and membrane-associated (DAG) second messengers. DAG recruits PKC to the membrane, where binding of calcium ions to PKC fully activates it. To accomplish this, IP3 promotes a transient increase of intracellular concentration by binding to a receptor on the endoplasmic reticulum, which opens a channel allowing release of stored calcium ions. PIP2, phosphatidylinositol 4,5-bisphosphate DAG, diacylglycerol PLC, phospholipase C IP3, inositol trisphosphate.

Gap junctional channels, like many other ion channels, can be modulated via second messengers and via phosphorylation processes. Besides these, intracellular calcium and pH have been proven to be important regulators of channel function. In this chapter the short-term regulatory processes are considered, i.e. processes on a time scale of minutes. Besides this, regulatory processes are known which take place over a period of 30 min up to several hours and which involve formation or synthesis of new gap junction channels. The latter processes are described in the following chapter. 

Second Law of Thermodynamics 284285 Second messengers 553 calcium ions 555 cyclic ADP-ribose 555 cyclic AMP 555 cyclic GMP 555... 

The large amount of work in this area reported by Russian workers and covered in our previous review [1] has also been reviewed by the Russian workers [284], These glycolipids have recently acquired a vastly increased biological interest since the discovery that various agonists at the cell surface stimulate a phospholipase which releases D-wiyo-inositol 1,4,5-trisphosphate from the membrane-bound phosphatidyl-inositol-4,5-bisphosphate. The released inositol trisphosphate acts as a second messenger by mobilising intra-cellular calcium ions [285-290]. 

Many extracellular ligands act by increasing the intracellular concentrations of second messengers such as cyclic adenosine-3, 5 -monophosphate (cAMP), calcium ion, or the phosphoinositides... 

---