Effectors, different types

The antiviral state induced by different types of IFNs is mediated by various IFN-induced proteins. The best-known antiviral effectors produced as a result of IFN cascade induction are shown in Table 2. They include 2 -5 oligoadenylate synthetase (2 -5 OAS), double-stranded RNA activated protein kinase (PKR), and myxovirus (Mx) proteins. Additional effectors include RNA-specific adenosine deaminase 1 (ADARl), the 20-kDa ISG product (ISG20), ISG54 and ISG56, and IFN-stimulated micro RNAs (Pedersen et al. 2007). 

The ai polypeptide contains the receptors for the Ca " channel effectors as it can be photolabelled by DHPs and PAAs [30,39-41,56,57,63] and various other Ca channel effectors. The other subunits do not appear to be required for proper binding of Ca channel effectors [64], although there is some evidence from biochemical studies that the other subunits may modulate binding [65]. The oti and y subunits are very hydrophobic, while the a.2jd and jS subunits are very hydrophilic [57]. The a [30], 2, 6 and y [57] peptides are glycosylated, but oc is much less so than 2 [30]. The of both a peptides varies slightly on different types of SDS gels... 

The neurotransmitters of the ANS and the circulating catecholamines bind to specific receptors on the cell membranes of effector tissue. Each receptor is coupled to a G protein also embedded within the plasma membrane. Receptor stimulation causes activation of the G protein and formation of an intracellular chemical, the second messenger. (The neurotransmitter molecule, which cannot enter the cell, is the first messenger.) The function of intracellular second messenger molecules is to elicit tissue-specific biochemical events within the cell that alter the cell s activity. In this way, a given neurotransmitter may stimulate the same type of receptor on two different types of tissue and cause two different responses due to the presence of different biochemical pathways within each tissue. 

G proteins transfer signals from 7-helix receptors to effector proteins (see above). G protein are heterotrimers consisting of three different types of subunit (a, 3, and y see p.224). The a-subunit can bind GDP or GTP (hence the name G protein ) and has GTPase activity. Receptor-coupled G proteins are related to other GTP-binding proteins such as Ras (see pp. 388, 398) and EF-Tu (see p. 252). 

One of the best-characterized effectors and second messenger systems is the cAMP cascade that can be either activated or inhibited by neurotransmit-ter/neuropeptide receptors, including those implicated in anxiety/stress such as CRE Receptors that activate cAMP synthesis couple with the stimulatory G protein, Gsa, and those that inhibit this second messenger couple with the inhibitory G protein, Gia, and these either stimulate or inhibit adenylyl cyclase, the effector enzyme responsible for synthesis of cAMP (Duman and Nestler 1999). There are at least nine different forms of adenylyl cyclase that have been identified by molecular cloning, each with a unique distribution in the brain. The different types of adenylyl cyclase are activated by Gsa as well as the diterpene forskolin, but are differentially regulated by Gia, the Py subunits, Ca, and by phosphorylation. This provides for fine control of adenylyl cyclase enzyme activity and regulation by other effector pathways. 

There are five different types of heavy chains, which correspond with five different classes of antibodies. The constant region of the heavy chain is identical in all antibodies of the same class. The classes of the immunoglobulin molecules differ based on the Fc region of the heavy chain, which are responsible for the different functions performed by each class. Thus the constant region confers on each class of antibody its effector function. 

Most receptors are protein macromolecules. When the agonist binds to the receptor, the proteins undergo an alteration in conformation which induces changes in systems within the cell that in turn bring about the response to the drug. Different types of effector-response exist. (1) The most swift are the channel-linked receptors, i.e. receptors coupled directly to membrane ion channels neurotransmitters... 

While the demonstration that the immune suppression by a given chemical is mediated by a metabolite, and not the parent compound, is an important observation, it does not in itself account for the mechanism of action. One indirect mechanism of action, which is consistent with a role for metabolism, involves a primary consequence of the generation of many reactive intermediates, that is, liver damage. Among many different types of adaptive responses, the liver is capable of secreting a number of soluble factors. Some of these soluble factors are capable of affecting immune responses. Most notably, as pointed out in Table 1, TGF- S is capable of modulating both T- and B-cell effector... 

The discovery of polarized subsets of CD4+ T cells that differ in their cytokine secretion pattern and effector functions has provided the molecular framework for the understanding of the diversity ofT-cell-dependent immune responses against different types of pathogens [63, 64], The two subsets of differentiated CD4+ T cells, T helper type 1 (Thl) and T helper type 2 (Th2), protect against different microbial pathogens by producing cytokines able to mobilize different mechanisms of defense. Thl cells are characterized by the secretion of interferon-y (IFN-y) and are adept at macrophage activation. 

Theories of interacting subunits are often referred to as allosteric theories, but the use of this word is unfortunate and should be avoided. The word allostery (Greek alios, other stereos, solid) refers to the possibility that substances (known as modifiers or effectors) can be attached at sites other than the site for the attachment of substrate. This is a completely different type of phenomenon and is of great importance in connection with the regulation of metabolic processes, but should be sharply distinguished from subunit interactions. However, in some enzymes the two effects are found together. 

The plasma includes numerous effectors (charged particles, UV photons, ROS, NOx, O3, etc.) and its composition varies depending on specific discharge conditions such as input power, gas composition, humidity and so on. Until now, the standardized correlations between the effectors and the responses do not exist and the plasma-induced effects are believed to be the device-specific consequences. What has been most studied amongst many factors is the plasma induced ROS. ROS has been identified as a predominant key factor in the plasma-induced cellular processes, and the majority of the research has shown the elevated level of intracellular ROS in cells or tissues (mostly epithelium) upon treatment by the APR. Surprisingly, our recent study on the stromal cells indicated that the intracellular ROS level was indeed reduced in the APP treated cells by the elevated antioxidant activities. Our result supports that cells of different types not only have different level of initial ROS but also have different level of ROS managing capacity via ROS scavenging process [Fig. 10]. Based on this, we concluded that the APP-cell interactions could be cell type specific (this cell type specificity, indeed, could be related to the selectivity of APP for cancer cells). Additional to the cell type sensitive properties, there are other variables, which make the plasma therapy... 

The values of the Hill coefficients for several membrane-bound enzymes from different sources (tissues) under the action of different types of effectors have been found to differ when the animals are fed either with an essential fatty acid supplemented diet or with a fat-free diet, respectively. The results which have been presented elsewhere (Farias et al., 1975) are summarized in Table 4. 

While competitive inhibition depends on a close structural relationship between the inhibitor and the normal substrate, certain enzymes may have their activity modified by metabolites which bear no structural relationship to the substrate and which bind reversibly to a site on the enzyme surface which is quite distinct from the substrate-binding site. This is known as the allosteric site. It is believed that allosteric regulators act by modifying the conformation of the active site so that it binds the substrate either more positive effectors or activators) or less negative effectors or inhibitors) strongly. The allosteric site is not necessarily close to the active site and may even be situated on a different type of subunit from the active site. 

At a cellular level, the activation of mAChRs leads to a wide spectrum of biochemical and electrophysiological responses [1, 5]. The precise pattern of responses that can be observed does not only depend on the nature of the activated G proteins (receptor subtypes) but also on which specific components of different signaling cascades (e.g. effector enzymes or ion channels) are actually expressed in the studied cell type or tissue. The observed effects can be caused by direct interactions of the activated G protein(s) with effector enzymes or ion channels or may be mediated by second messengers (Ca2+, DP3, etc.) generated upon mAChR stimulation. 

---