Second messengers 3-diphosphate

The most common second messenger activated by protein/peptide hormones and catecholamines is cyclic adenosine monophosphate (cAMP). The pathway by which cAMP is formed and alters cellular function is illustrated in Figure 10.1. The process begins when the hormone binds to its receptor. These receptors are quite large and span the plasma membrane. On the cytoplasmic surface of the membrane, the receptor is associated with a G protein that serves as the transducer molecule. In other words, the G protein acts as an intermediary between the receptor and the second messengers that will alter cellular activity. These proteins are referred to as G proteins because they bind with guanosine nucleotides. In an unstimulated cell, the inactive G protein binds guanosine diphosphate (GDP). When the hormone... 

There are several intracellular second messengers that are activated by metabotropic receptors, also referred to as G protein-coupled receptors (Duman and Nestler 1999). These receptors couple with G proteins that are heterotrimers made up of a-, (3- and y-subunits. Interaction of the G protein heterotrimer with activated receptor increases the exchange of guanosine triphosphate (GTP) for bound guanosine diphosphate (GDP), resulting in dissociation of the heterotrimer into free a and (3y subunits that in turn can regulate second messen-... 

Fig. 1. A compact visual summary of the signaling of cytoplasmic/nuclear and cell surface receptors. ER, endoplasmic reticulum M, mitochondrion PIP2, phosphatidylinositol-4,5-diphosphate IP3, inositol triphosphate PK, protein kinase, second messenger.

Dousa TP, Chini EN, and Beers KW (1996) Adenine nucleotide diphosphates emerging second messengers acting via intracellular Ca + release. American Journal of Physiology 271, C1007-24. 

Dousa, T. P, Chini, E. N., and Beers, K. W. (1996). Adenine nudeolide diphosphates Emerging second messengers acting via intracellular Ca release. Am, /. FhysioL 271, C1007-G1024. 

Cyclic adenosine 5 diphosphate ribose. This is another second messenger involved with the release of Ca + (11.86c) [25]. 

Prod, in vivo by hydrol. of phosphatidylinositol 4,5-diphosphate. Present in mammalian brain tissue. Important cellular second messenger. Controls Ca release from intracellular stores. Cryst. (MeOH aq.) (as tri-Na salt), [a] -11.1 (c, 0.9 in H2O) (tri-Na salt). Mp >270° (as tri-Na salt). Chiral, D-form. 

Figure 2. The so-called canonical phosphoinositide pathway . The continuous phosphorylation/dephosphorylation reactions allow a steady-state level of Ptdins, PtdIns(4)P and PtdIns(4,5)P2 in the plasma membrane (PM). Cleavage of PtdIns(4,5)P2 by phospholipase C (PLC) generates the two well-known second messengers, inositol 1,4,5-trisphosphate (Ins(l,4,5)P3) and diacylglycerol (DAG). Besides its role as a protein kinase C (PKC) activator, DAG can be phosphorylated to phosphatidic acid (PA). The resynthesis of Ptdins from inositol and PA occurs mainly in the endoplasmic reticulum (ER). PPi, inorganic phosphate. PA-Pase, phosphatidic acid phosphatase. PA-TP, phosphatidic acid transport protein. PtdIns-TP, phosphatidylinositol transport protein. CDP-DAG, cytidine diphosphate-diacylglycerol. CMP, CDP and CTP, cytidine mono-, di- and triphosphate, respectively.

Mvo-inositol 1,4-diphosphate (38), the racemate of a metabolite of second messenger myo-inositol 1,4,5-triphosphate and its diphosphorothioate analogue (39) have been synthesised from f 1 -1 2.4 S-di-O-isopropylidene-mvo-inositol by way of phosphite intermediates. Similarly, (-mvo-inositol 1,3,4-triphosphate has been obtained from f W2.4.S-tri-O-benzyl-myo-inositol Phosphite chemistry was also employed in the preparation of diphosphorylated and diphosphonylated Lipid A monosaccharide analogues (40). Related Lipid A components are mentioned in Chapter 9. Methyl 3-deoxv-a-D-manno-oct-2-ulopyranosidonic acid 4-phosphate has been synthesised and its chemical stability studied. ... 

There have been further papers related to the second messenger cyclic adenosine 5 -diphosphate ribose (cADPR). Potter s laboratory has reported that the enzyme which cyclizes NAD to cADPR will also produce analogues of cADPR from NAD analogues with modifications in the adenosine unit (2 - or 3 -deoxycompounds, 8-substituents, and the formycin isostere), whilst Sih and co-workers have shown the enzymic cyclization of NADP to cADPR phosphate 3 -NADP and 2, 3 -cyclic NADP also were converted to the cADPR derivatives. The cyclase enzyme has been shown to convert the guanine and hypoxanthine analogues of NAD into products 164 (X=NH2 or H) containing a 7-1" link, as opposed to the 1-1" link in cADPR. The same sort of 7-1" link is formed on enzymic cyclization of l,N -etheno-NAD. ... 

The muscarinic receptors are considered to be part of the superfamily of G protein-coupled receptors. They consist of seven transmembrane helices and are linked to their G protein through interaction with the second and third intracellular loops (25). There are five subtypes of receptor, designated M1-5, and the odd-numbered receptors (Mi, M3, and Ms) are coupled to the Gq/Gn class. This class of receptors activate intracellular phospholipase C to hydrolyze phosphatidylinositol 4,5-diphosphate to diacylglycerol and inositol triphosphate as intracellular messengers. The even-numbered receptors (M2 and M4) are coupled to the Gi/Go class, which mediates the inhibition of adenylate cyclase (Fig. 44.14). 

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