Receptors Located on the Cells Surface

Purines such as ATP and adenosine play a central role in the energy metabolism of all life forms. This fact probably delayed recognition of other roles for purines as autocrine and paracrine substances and neurotransmitters. Today it is recognized that purines are released from neurons and other cells and that they produce widespread effects on multiple organ systems by binding to purinergic receptors located on the cell surface. The principal ligands for... 

Growth factor receptors located on the cell surface are often water-soluble because the peptide growth factors cannot diffuse across the plasma membrane... 

Hence, steroids exert their primary effects by acting on receptors located within the cell. As discussed in Chapter 4, it is apparent that these substances exert some of their effects by binding to a second set of receptors located on the cell surface.1318 Studies continue to define the exact role of steroidal surface receptors and their contribution to the effects of each type of steroid... 

The extrinsic pathway consists of a series of events initially induced by death receptors located on the cell surface. It is initiated by interaction of extracellular death ligands with their respective receptors, located on the surface of the plasma membrane. The death ligands are members of the tumor necrosis factor (TNF)/nerve growth factor (NGF) superfamily. TNF-R1, Fas (Apo-l/CD95), TRAIL-R1, TRAIL-R2, and NGF-R are examples of death receptors. They are transmembrane proteins consisting of an external domain, where the ligand associates, and a cytoplasmic domain, which contains the DD (death domain). 

Most receptors (a notable exception being the steroid receptors that influence DNA transcription) are located on the cell surface, and purified cell membranes are thus an obvious choice of preparation. When a tissue is homogenized, however, any membrane fraction isolated may well contain membranes from intracellular organelles in addition to cell membranes from all the cell types present in the tissue. Thus, brain membranes will contain membranes not only from neurons but... 

The binding of a hormone to its receptor initiates intracellular events that direct the hormone s action. Ultimately, all hormones produce their effects by altering intracellular protein activity. However, the mechanism by which this occurs depends on the location of the hormone receptor. Receptors are typically located on the cell surface or in the cell nucleus. As a result, most hormones carry out their effects by means of two general mechanisms ... 

The P-site of adenylyl cyclase inhibits cyclic AMP accumulation. Since P, and P2 receptors are located on the cell surface, they bind purines or pyrimidines in the extracellular space. There also is an adenosine binding site located intracellularly on the enzyme adenylyl cyclase (see Ch. 21). This is referred to as the P-site of adenylyl cyclase. Binding of adenosine and other purines, notably 3 AMP, 2 deoxy-3 -ATP and 2, 5 -dideoxyadenosine to this site, inhibits adenylyl cyclase activity [8]. The P-site of adenylyl cyclase and other intracellular purine binding sites are not classified as purinergic receptors. 

The receptors can either be located on the cell surface or within the cell. Not surprisingly, the mechanisms of the effector systems are, in principle, quite distinct for the two... 

Immunoglobulin M (IgM), a membrane protein on the surface of B lymphocytes, serves to bind free antigens to the B cells. By contrast, T cell receptors only bind antigens when they are presented by another cell as a complex with an MHC protein (see below). Interaction between MHC-bound antigens and T cell receptors is supported by co-recep-tors. This group includes CDS, a membrane protein that is typical in cytotoxic T cells. T helper cells use CD4 as a co-receptor instead (not shown). The abbreviation CD stands for cluster of differentiation. It is the term for a large group of proteins that are all located on the cell surface and can therefore be identified by antibodies. In addition to CD4 and CDS, there are many other co-receptors on immune cells (not shown). 

The most popular OTC sleep aids are those that contain antihistamines such as diphenhydramine or doxylamine (Table 3.1). As noted in Chapter 1, nerve cells in the brain communicate with each other by secreting chemicals called neurotransmitters. One such neurotransmitter that regulates sleep is histamine. When histamine is released by a nerve cell, it diffuses over to the target nerve cell and binds to specialized proteins called receptors located on the outer surface of the nerve cell. These receptors are specially designed to bind only histamine, and when they do, the target nerve cell will become either activated or deactivated. In the brain, histamine serves the function of keeping us awake, and when drugs such as antihistamines are taken, they block the ability of histamine receptors to bind histamine. 

Peptide-hormones like hypothalamus-pituitary, gastrointestinal, parathyroid, neurohormones, Gfs related peptide-hormones cannot penetrate the plasma membrane and their receptors are located on the cell surface and the signal transport to the nucleus is becoming via a second messenger. The main hormone action seems to be DNA synthesis whereas other including mediation of neurotransmission, enzyme synthesis, regulation and synthesis of structural proteins are responsible for the specific characteristics of differentiated cell. 

Interaction of OA with a specific receptor located on the surface of the responding cell or on the presynaptic membrane of the releasing cell. 

Mechanism of Action-. A selective vascular endothelial growth factor (VEGF) antagonize that selectively binds and activates receptors located on the surface of vascular endothelial cells. Therapeutic Effect Blocks angiogenesis and vascular permeability and inflammation which contribute to the progression of the neovascular (wet) form of age-related macular degeneration (AMD). 

Receptor tyrosine kinases possess binding sites at the surface of the cell membrane that are specific for extracellular ligands. Ligand binding to the receptor activates a tyrosine-specific protein kinase activity of the receptor, located on the cytoplasmic domain. Consequently, tyrosine phosphorylation is initiated, at the receptor itself and also on substrate proteins these in turn trigger the biological response of the cell by... 

Rather than direcdy affecting membrane permeability or directly influencing enzyme activity, other membrane receptors affect cell function by linking to an intermediate regulatory protein that is located on the inner surface of the cell s membrane.2,23,45 These regulatory proteins are activated by binding guanine... 

PTH is a polypeptide hormone that is synthesized within the cells of the parathyroid glands. The primary factor controlling the release of PTH is the amount of calcium in the bloodstream.36 A calciumsensing receptor is located on the outer surface of the parathyroid cell membrane, and this receptor monitors plasma calcium levels.11,88 A decrease in plasma calcium activates this receptor and causes increased release of PTH. As blood calcium levels increase, the receptor is inhibited, and PTH release is reduced. 

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