Cell membrane receptors

The smooth muscle cell does not respond in an all-or-none manner, but instead its contractile state is a variable compromise between diverse regulatory influences. While a vertebrate skeletal muscle fiber is at complete rest unless activated by a motor nerve, regulation of the contractile activity of a smooth muscle cell is more complex. First, the smooth muscle cell typically receives input from many different kinds of nerve fibers. The various cell membrane receptors in turn activate different intracellular signal-transduction pathways which may affect (a) membrane channels, and hence, electrical activity (b) calcium storage or release or (c) the proteins of the contractile machinery. While each have their own biochemically specific ways, the actual mechanisms are for the most part known only in outline. 

Adenosine exerts its cellular effects through G-protein-coupled cell membrane receptors, which are divided into classes Ai, A2a. A2B, and A3 (for reviews, see Fredholm, 1995 Haas Selbach, 2000 Dunwiddie Masino, 2001). Ai (A, R)... 

Burnstock, G. A basis for distinguishing two types of purinergic receptor. In L. Bolis and R. W. Straub (eds), Cell Membrane Receptors for Drugs and Hormones A Multidisciplinary Approach. New York Raven Press, pp. 107-118,1978. 

Bioreceptors Antibodies Lectins Cell membrane receptors Nucleic acids Synthetic molecules... 

Receptor In cell membrane Receptor inside cell... 

In cells that use Ca + as second messenger, binding of an external signal to a cell membrane receptor activates phospholipase C (PLC), which, in turn, synthesizes inositol 1,4,5-trisphosphate (InsP3). This metabolite binds to an InsP3 receptor located on the membrane of internal Ca + stores (endoplasmic or sarcoplasmic reticulum) and thereby triggers the release of Ca " " into the cytoplasm of the cell [56]. A conspicuous feature of Ca release is that it is self-amplified Cytosohc Ca + triggers the release of Ca " " from intracellular stores into the cytosol, a process known as Ca +-induced Ca " " release (CICR) [57, 58]. 

Fig. 14. Effects of temperature on the absorbance of hemopexin and the N-domain of hemopexin. The unfolding of hemopexin and N-domain in 25 mM sodium phosphate, pH 7.4, was examined using absorbance spectroscopy (N. Shipulina et al., unpublished). The second derivative UV absorbance spectra of the protein moieties were used to follow protein unfolding and the Soret and visible region spectra to monitor the integrity of the heme complexes, as done with cytochrome 6502 (166). The ferri-heme complex is more stable than the apo-protein moiety, but the is slightly lower than that assessed by DSC, indicating that changes in conformation occur before thermodynamic unfolding. Reduction causes a large decrease in heme-complex stabihty, which is proposed to be a major factor in heme release from hemopexin by its cell membrane receptor, and addition of 150 mM sodium chloride enhanced the stabihty of ah forms of hemopexin.

Figure 4.3 A prototype signal protein and its receptor is illustrated here. The human body relies on hundreds of different signal proteins docking into very specific and selective cell membrane receptor proteins to control which cell proteins are made or broken down and how the cell functions by sending specific chemical signals to other parts of the cell. The signal proteins may be produced by a nearby cell or reach its target from a distant cell through the blood stream.

Calcineurin is part of a signaling pathway that is activated by a rise in intracellular calcium upon ligand binding to a cell membrane receptor. The rise in Ca activates calcineurin s phosphatase activity, which dephosphorylates cytoplasmic NF-AT transcription factor family members. Dephosphorylated NF-AT-members enter the nucleus and bind to DNA in cooperation with other transcription factors, e.g. AP-1. By this way many target genes in diverse tissues can be activated. 

Prompt effects such as initial feedback suppression of pituitary ACTH occur in minutes and are too rapid to be explained on the basis of gene transcription and protein synthesis. It is not known how these effects are mediated. Among the proposed mechanisms are direct effects on cell membrane receptors for the hormone or nongenomic effects of the classic hormone-bound glucocorticoid receptor. The putative membrane receptors might be entirely different from the known intracellular receptors. 

Irvine, R.F. (1997). Talking to cells—cell membrane receptors and their modes of action. Foundations of Modem Biochemistry, Vol. 3, pp. 173-201. JAI Press, Greenwich, CT. 

S. V. Perry. Three Hundred Years of Bacterial Motility, Judith P. Armitage. Talking to Cells-Cell Membrane Receptors and Their Modes of Action, Robin F. Irvine. Mechanisms in Regulation Protein Phosphorylation, Philip J. Randle. Regulation of Expression of Microbial Genes, Patricia H. Clarke. Antibody Specificity and Diversity The Proteins (Part I), Lisa A. Steiner. Author Index. Subject Index. 

Hajjar, K.A., 1993, Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor. J. Clin. Invest 91, 2873-2879. 

The extracellular domain of cell membrane receptors can be produced recombi-nantly and used as a therapeutic product. The soluble receptor can be used to bind and neutralize the receptor s endogenous ligands (e.g., etanercept), or it can be used for stimulation of a co-receptor (e.g., abatacept). Soluble receptors are typically produced as IgG Fc fusion proteins to extend the half-life of the receptor in circulation. 

Specific domains of proteins (for example, those mentioned in the section Organic Phase ) adsorbed to biomaterial surfaces interact with select cell membrane receptors (Fig. 8) accessibility of adhesive domains (such as specific amino acid sequences) of select adsorbed proteins may either enhance or inhibit subsequent cell (such as osteoblast) attachment (Schakenraad, 1996). Several studies have provided evidence that properties (such as chemistry, charge, and topography) of biomaterial surfaces dictate select interactions (such as type, concentration, and conformation or bioactivity) of plasma proteins (Sinha and Tuan, 1996 Horbett, 1993 Horbett, 1996 Brunette, 1988 Davies, 1988 Luck et al., 1998 Curtis and Wilkinson, 1997). Albumin has been the protein of choice in protein-adsorption investigations because of availability, low cost (compared to other proteins contained in serum), and, most importantly, well-documented conformation or bioactive structure (Horbett, 1993) recently, however, a number of research groups have started to examine protein (such as fibronectin and vitronectin) interactions with material surfaces that are more pertinent to subsequent cell adhesion (Luck et al., 1998 Degasne et al., 1999 Dalton et al., 1995 Lopes et al., 1999). 

NPs have physical dimensions close to cell membrane receptors and other biomolecules. This opens a new scenario to be explored. For example, the small dimensions are responsible for an enhanced penetrability of the cell membrane, since endocytosis is favored. The interaction with proteins is also affected by dimensions differences in surface curvature influence the ability of proteins to interact with surface functionalities, and consequently possible differences in conformational modification may occur.13 This is particularly relevant in the case of enzymes, where activity may depend on conformation. 

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