Showing papers on "Receptor published in 1981"

Bacterial Adherence: Adhesin-Receptor Interactions Mediating the Attachment of Bacteria to Mucosal Surfaces

Abstract: Recent studies have indicated that the attachment of bacteria to mucosal surfaces is the initial event in the pathogenesis of most infectious diseases due to bacteria in animals and humans. An understanding of the mechanisms of attachment and a definition of the adhesive molecules on the surfaces of bacteria (adhesins) as well as those on host cell membranes (receptors) have suggested new approaches to the prevention of serious bacterial infections: (1) application of purified adhesion or receptor materials or their analogues as competitive inhibitors of bacterial adherence; (2) administration of sublethal concentrations of antibiotics that suppress the formation and expression of bacterial adhesins; and (3) development of vaccines against bacterial surface components involved in adhesion to mucosal surfaces. Progress has already been made in the development of antiadhesive vaccines directed against the fimbrial adhesins of several human bacterial pathogens.

T cell growth factor receptors. Quantitation, specificity, and biological relevance

Abstract: To examine directly the hypothesis that T cell growth factor (TCGF) interacts with target cells in a fashion similar to polypeptide hormones, the binding of radiolabeled TCGF to various cell populations was investigated. The results indicate that TCGF interacts with activated T cells via a receptor through which it initiates the T cell proliferative response. Internally radiolabeled TCGF, prepared from a human T leukemia cell line and purified by gel filtration and isoelectric focusing, retained biological activity and was uniform with respect to size and charge. Binding of radiolabeled TCGF to TCGF-dependent cytolytic T cells occurred rapidly (within 15 rain at 37 degrees C) and was both saturable and largely reversible. In addition, at 37 degrees C, a receptor- and lysosome-dependent degradation of TCGF occurred. Radiolabeled TCGF binding was specific for activated, TCGF-responsive T cells. Whereas unstimulated lymphocytes of human or murine origin and lipopolysaccharide-activated B cell blasts expressed few if any detectable binding sites, lectin- or alloantigen-activated cells had easily detectable binding sites. Moreover, compared with lectin- or alloantigen-activated T cells, long-term TCGF-dependent cytolytic and helper T cell lines and TCGF-dependent neo-plastic T cell lines bound TCGF with a similar affinity (dissociation constant of 5-25 pM) and expressed a similar number of receptor sites per cell (5,000-15,000). In contrast, a number of TCGF-independent cell lines of T cell, B cell, or myeloid origin did not bind detectable quantities of radiolabeled TCGF. Binding of radiolabeled TCGF to TCGF-responsive cells was specific, in that among several growth factors and polypeptide hormones tested, only TCGF competed for binding. Finally, the relative magnitude of T cell proliferation induced by a given concentration of TCGF closely paralleled the fraction of occupied receptor sites. As the extent of T cell clonal expansion depends on TCGF and on the TCGF receptor, the dissection of the molecular events surrounding the interaction of TCGF and its receptor that these studies permit, should provide new insight into the hormonelike regulation of the immune response by this lymphokine.

Opposing roles for D-1 and D-2 dopamine receptors in efflux of cyclic AMP from rat neostriatum.

Abstract: Two types of dopamine receptor whose stimulation affects cellular cyclic AMP have now been identified. In tissues as different as insect ganglia and mammalian neostriatum, stimulation of the dopamine receptor called D-1 increases formation of cyclic AMP1–6, whereas stimulation of the second type of dopamine receptor (D-2)7–11, first identified in the rat pituitary gland, reduces cyclic AMP formation. Recently, a receptor with the pharmacological properties of the D-2 receptor has also been found12–14 in the rat neostriatum; we show here that stimulation of this receptor is followed by a reduction in cyclic AMP formation induced by V stimulation with D-1 agonists.

Regulation of plasma cholesterol by lipoprotein receptors

Abstract: The lipoprotein transport system holds the key to understanding the mechanisms by which genes, diet, and hormones interact to regulate the plasma cholesterol level in man. Crucial components of this system are lipoprotein receptors in the liver and extrahepatic tissues that mediate the uptake and degradation of cholesterol-carrying lipoproteins. The number of lipoprotein receptors, and hence the efficiency of disposal of plasma cholesterol, can be increased by cholesterol-lowering drugs. Regulation of lipoprotein receptors can be exploited pharmacologically in the therapy of hypercholesterolemia and atherosclerosis is man.

GABA‐Benzodiazepine‐Barbiturate Receptor Interactions

Abstract: The major inhibitory neurotransmitter in mammalian brain, y-aminobutyric acid (GABA), exerts its effects through increased postsynaptic membrane permeability to chloride ions (McBurney and Barker, 1978; Nistri et a]., 1980). The GABA receptor and associated chloride ion channel appear to be part of a protein complex containing receptor sites for GABA, benzodiazepines, and picrotoxininl barbiturates, as well as the chloride ionophore (Fig. 1). The three types of drug receptor sites studied by radioactive ligand binding have been thoroughly characterized to show their relevance to in vivo actions of the drugs that bind to the receptor sites in v i m . Various lines of evidence support the hypothesis that modulation of the postsynaptic response to GABA is involved in many of the actions of both the benzodiazepines (Haefely et a]., 1979; Costa and Guidotti, 1979) and the barbiturates and related central nervous system depressants (Nicoll et al., 1975; Haefely et a]., 1979; Macdonald and Barker, 1979). This article reviews the recent evidence for in v i m interactions between the three categories of drug receptors; the evidence supports the model for a complex as depicted in Fig. 1 and thus the relevance of GABA to the actions of the other drugs.

Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin.

Abstract: A murine monoclonal antibody (OKT9) raised against human leukemic cells binds to a wide variety of leukemia and tumor cell lines and to a minority of leukemia cells taken directly from patients Fetal thymus and liver are strongly reactive as are some normal, immature hemopoietic cells and activated lymphocytes Reactivity with OKT9 appears to correlate with proliferation status in both normal and malignant populations Biochemical analysis indicates that this structure is a approximately equal to 180,000-dalton glycoprotein with two disulfide-bonded subunits of approximately equal to 90,000-daltons Isolation of the transferrin receptor from a T-cell line (MOLT-4) indicates that it also has a dimeric approximately equal to 180,000-dalton structure Radio-labeled transferrin bound to its receptors can be specifically precipitated by the monoclonal OKT9, although the latter does not bind transferrin itself, indicating that the antigenic structure defined by this antibody is likely to be the transferrin receptor

Characterization of Several Clonal Lines of Cultured Ley dig Tumor Cells: Gonadotropin Receptors and Steroidogenic Responses*

Abstract: Several clonal lines of cultured Leydig tumor cells have been established and characterized in terms of gonadotropin receptors and steroid production. Although freshly isolated cells derived from the M5480P tumor have functional hCG receptors, only two of the five clonal lines established were shown to bind significant quantities of hCG. In these clones, steroid production can be stimulated to the same extent by hCG, cholera toxin, and 8-Br-cAMP. The other three clones bind a small amount of hCG and respond to the hormone with a marginal increase in steroidogenesis. Steroid production, however, is significantly stimulated by cholera toxin or 8-Br-cAMP. A comparison of the steroids produced by freshly isolated cells and two of the clones revealed some changes in the steroidogenic pathway. The most obvious change is an increase in the ability of the cultured cells to synthesize 20α-dihydroprogesterone (20α-hydroxypregn-4-en-3-one). These clonal lines may provide a suitable model system for the study of gona...

1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture.

Abstract: In this study we demonstrate the presence of specific, high-affinity receptors for 1,25-dihydroxyvitamin D3 in malignant melanoma. Receptors are present both in cultured melanoma cells and in melanoma tumor tissue produced by inoculation of cells into athymic rats. The receptor sediments at 3.25 on sucrose density gradients, possesses a preferential affinity for 1,25-(OH)2D3 and has an apparent Kd of 0.18 nM by Scatchard analysis. We also demonstrate that human melanoma cells are responsive to 1,25-(OH)2D3 in vitro. Inclusion of 1,25-(OH)2D3 in the culture medium produced a marked increase in cell doubling time. This inhibitory effect of the hormone on melanoma cell proliferation was dose-related and represents the first demonstration of a 1,25-(OH)2D3 mediated action on tumor cells.

Evidence that types I and II interferons have different receptors.

Abstract: Interferons (IFNs) are a class of proteins, secreted by animal cells in response to various inducers1, which confer resistance to viral infections and are designated according to their cellular origin or to the inducing agent. Viruses induce type I Interferon, subdivided into α-interferon, produced by leukocytes (Le) or lymphoblastoid (Ly) cells, and β-interferon, produced by fibroblasts1. Mitogens and antigenic stimuli induce in lymphocytes type II immune IFN-γ. Interferons seem to bind to specific receptors2 to elicit a variety of cellular responses3; several early studies provided indirect evidence for such binding4–6. Direct evidence for specific interferon receptors was presented by Aguet7, who showed that biologically active 125I-labelled mouse (Mu)IFN binds to sensitive L1210-S cells, but not to interferon-resistant L1210-R cells8. The main obstacle in carrying out such studies is the availability of pure interferon. Recently, Maeda et al.9 constructed plasmids containing human interferon sequences. The plasmid p104 was used as a probe to isolate the coding region of a human interferon (IFLrA), which was expressed in Escherichia coli10 and purified with monoclonal antibodies11. This interferon, designated HuIFN-αA, was labelled with 125I for binding assays on human cells. We have determined the specificity of different HuIFNs for the cellular sites which bind HuIFN-αA and show here that HuIFN-γ does not compete for binding, whereas all type I HuIFNs do.

The stimulation of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: defined characteristics and unanswered questions.

Abstract: It now appears to be generally agreed that the 'phosphatidylinositol response', discovered in 1953 by Hokin & Hokin, occurs universally when cells are stimulated by ligands that cause an elevation of the ionized calcium concentration of the cytosol. The initiating reaction is almost certainly hydrolysis of an inositol lipid by a phosphodiesterase. Phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate all break down rapidly under such circumstances. However, we do not yet know which of these individual reactions is most closely coupled to receptor stimulation, nor do we know where in the cell it occurs. With many stimuli, inositol phospholipid breakdown is closely coupled to occupation of receptors and appears not to be a response to changes in cytosol [Ca2+]: this provoked the suggestion that it may be a reaction essential to the coupling between activation of receptors and the mobilization of Ca2+ within the cell. In a few situations, however, it appears probable that inositol lipid breakdown can occur as a result of the rise in cytosol [Ca2+] that follows receptor activation: such observations gave rise to the alternative opinion that inositol lipid breakdown cannot be related to stimulus-response coupling at calcium-mobilizing receptors. It now seems likely that these two views are too rigidly polarized and that some cells probably display both receptor-linked and Ca2+-controlled breakdown of inositol lipids. Both may sometimes occur simultaneously or sequentially in the same cell.

Specific receptors for platelet-derived growth factor on cells derived from connective tissue and glia.

Abstract: A cellular receptor for platelet-derived growth factor (PDGF) was demonstrated by incubation of 125I-labeled PDGF with human foreskin fibroblast cultures followed by liberation of cell-bound radioactivity with Triton X-100. The cellular binding of labeled PDGF in the presence of increasing amounts of unlabeled PDGF showed saturation; Scatchard analysis of binding data indicated a single class of receptors having kd = 1 X 10(-9) M. The number of PDGF binding sites was approximately 3 X 10(5)/cell. Labeled PDGF binding reached an apparent equilibrium after 3 hr at 4 degrees C. At 37 degrees C, it passed a maximum after 30 min and then decreased with time due to degradation of the tracer. A large excess of unlabeled PDGF reduced labeled PDGF binding by more than 90% whereas similar doses of epidermal growth factor, fibroblast growth factor, or insulin had no effect. It was concluded that PDGF did not share receptors with these factors. PDGF receptors were found on skin fibroblasts, normal and malignant glial cells, smooth muscle cells, and 3T3 cells but not on epithelial-derived cells, neuroblastoma cells, endothelial cells, or peripheral lymphocytes.l As only the receptor-positive cells--i.e., the connective tissue- and glia-derived cells--are responsive to stimulation with PDGF, these findings imply a functional significance of the PDGF receptor.

The mast cell.

Abstract: The mast cell is the cellular basis for immediate hypersensitivity reactions. The specificity of the immediate hypersensitivity reaction is attributable to IgE molecules fixed to specific membrane receptors which, when stimulated by specific antigen, initiates the process of degranulation of the mast cell. The granules provide three separate sources of biologic activity: performed or primary mediators, newly generated or secondary mediators, and activities associated with the granular matrix. A number of biologic consequences are generated in response to these mediators and these include: increased vascular permeability, vasodilation, smooth muscle spasm, polymorphonuclear leukocyte chemotaxis, stimulation of adenylate and guanylate cyclase, superoxide radical generation, prostaglandin formation, mucous and gastric acid secretion, hypotension, tissue destruction, and mononuclear leukocyte infiltration. This pharmacopia of activities accounts for the clinical aspects of allergic diseases, suggests that the mast cell granule may be involved in the host's defense against parasitic infections, and is compatible with a suggested role of the mast cell as a widely distributed, monocellular endocrine system.

Specific receptor for the opioid peptide dynorphin: structure--activity relationships.

Abstract: The structural features responsible for the high potency and opiate receptor specificity of the opioid peptide dynorphin in the guinea pig ileum myenteric plexus were examined. Successive removal of COOH-terminal amino acids from dynorphin-(1--13) demonstrated important contributions of lysine-13, lysine-11, and arginine-7 to the potency. Removal of the NH2-terminal tyrosine abolished the biologic activity. Several other structural modifications were shown to affect potency: substitution of D-alanine for glycine-2 reduced the potencies of dynorphin-(1--13) amide, -(1--11), and -(1--10); and methyl esterification of the COOH terminus enhanced the potencies of dynorphin-(1--12), -(1--10), -(1--9), -(1--8), and -(1--7). Within the dynorphin sequence, lysine-11 and arginine-7 were found to be important for selectivity of interaction with the dynorphin receptor, which is distinguishable from the mu receptor in this tissue.

Identification of a human T lymphocyte surface protein associated with the E-rosette receptor.

Abstract: We describe a new monoclonal murine antibody that reacts with a 50,000-mol wt polypeptide that appears to be present on all E-rosetting cells. We conclude that this antigen is either identical to or closely associated with the E receptor because of (a) the high degree of concordance between E-rosette formation and 9.6 antigen expression, (b) the inhibition of rosette formation by preincubation of cells with 9.6 antibody, and (c) the observed failure of cells lysostripped of 9.6 antigen to form E-rosettes. This last finding suggests cocapping of 9.6 antigen and the E receptor.

Agonist and antagonist benzodiazepine receptor interaction in vitro

Abstract: A representative of a novel series of imidazodiazepines, Ro 15-1788, selectively antagonizes all major central actions of benzodiazepines by competitive, high-affinity interactions with benzodiazepine receptors (BR) in the central nervous system (CNS)1–3. Doses of Ro 15-1788 sufficient to antagonize benzodiazepine actions have been shown per se to lack phamacological action in animals and man1–4. Thus Ro 15-1788 provides a highly selective tool for experimental investigations of BR-mediated events and is of therapeutic value in all cases where a rapid termination of benzodiazepine actions is indicated. Using 3H-labelled Ro 15–1788 as radioligand in equilibrium binding studies in vitro, we show here that 3H-Ro 15-1788 interacts with the same number of BR sites as the agonist 3H-clonazepam in various brain regions. However, their mode of receptor interaction is different. In conditions which alter receptor affinity for 3H-clonazepam binding, such as addition of γ-aminobutyric acid (GABA) or certain ions, no change is seen in 3H-Ro 15-1788 binding. This effect can be used to distinguish between benzodiazepine receptor agonists and antagonists in vitro. Furthermore, the thermodynamics of agonist and antagonist receptor interaction are different, but only at temperatures above 21 °C.

Regulatory role for hepatic low density lipoprotein receptors in vivo in the dog

Abstract: Liver membranes from young beagle dogs were found to possess binding sites that resemble the low density lipoprotein (LDL) receptors originally described in cultured human fibroblasts. Treatment of the dogs with colestipol (a bile acid sequestrant) and mevinolin (a cholesterol synthesis inhibitor) produced a 3-fold increase in LDL binding activity. This increase correlated with a 2-fold increase in the fractional catabolic rate for intravenously administered human or canine 125I-labeled LDL, suggesting that the increased hepatic receptors were responsible for the enhanced clearance of LDL from plasma. The hepatic lipoprotein receptors of control and drug-treated dogs resembled human fibroblast LDL receptors in that they bound apoprotein E-containing lipoproteins, such as very low density lipoproteins and a subfraction of high density lipoproteins (HDL1), with 10-fold higher affinity than the apoprotein B-containing lipoprotein LDL; failed to bind canine HDL2 and human HDL3, which are devoid of apoproteins B and E; failed to bind methylated LDL; required calcium; and were destroyed by Pronase. Treatment of dogs with mevinolin not only increased the fractional catabolic rate for LDL but also reduced the synthetic rate for the lipoprotein. The current data suggest that the liver of dogs contains functional LDL receptors that are susceptible to metabolic regulation and that a drug-induced increase in the activity of these receptors can contribute to a lowering of plasma levels of LDL-cholesterol.

Receptor for albumin on the liver cell surface may mediate uptake of fatty acids and other albumin-bound substances.

Abstract: Kinetic analysis of the uptake of carbon-14-labeled oleate in a single-pass perfusion of rat liver and saturable and specific binding of iodine-125-labeled albumin to hepatocytes in suspension suggest the existence of a receptor for albumin on the liver cell surface. The putative receptor appears to mediate uptake of albumin-bound fatty acids by the cell and may account for the efficient hepatic extraction of many other substances tightly bound to albumin.

Two independent lipoprotein receptors on hepatic membranes of dog, swine, and man. Apo-B,E and apo-E receptors.

Abstract: We have reported previously that canine livers possess two distinct lipoprotein receptors, an apoprotein (apo)-B,E receptor capable of binding the apo-B-containing low density lipoproteins (LDL) and the apo-E-containing cholesterol-induced high density lipoproteins (HDLc), and an apo-E receptor capable of binding apo-E HDLc but not LDL. Both the apo-B,E and apo-E receptors were found on the liver membranes obtained from immature growing dogs, but only the apo-E receptors were detected on th hepatic membranes of adult dogs. In this study, the expression of the apo-B,E receptors, as determined by canine LDL binding to the hepatic membranes, was found to be highly dependent on the age of the dog and decreased linearly with increasing age. Approximately 30 ng of LDL protein per milligram of membrane protein were bound via the apo-B,E receptors to the hepatic membranes of 7- to 8-wk-old immature dogs as compared with no detectable LDL binding in the hepatic membranes of adult dogs (greater than 1--1.5 yr of age). Results obtained by in vivo turnover studies of canine 125I-LDL correlated with the in vitro findings. In addition to a decrease in the expression of the hepatic apo-B,E receptors with age, these receptors were regulated, i.e., cholesterol feeding suppressed these receptors in immature dogs and prolonged fasting induced their expression in adult dogs. Previously, it was shown that the apo-B,E receptors were induced in adult livers following treatment with the hypocholesterolemic drug cholestyramine. In striking contrast, the apo-E receptors, as determined by apo-E HDLc binding, remained relatively constant for all ages of dogs studied (10--12 ng/mg). Moreover, the expression of the apo-E receptors was not strictly regulated by the metabolic perturbations that regulated the apo-B,E receptors. Similar results concerning the presence of apo-B,E and apo-E receptors were obtained in swine and in man. The hepatic membranes of adult swine bound only apo-E HDLc (apo-E receptors), whereas the membranes from fetal swine livers bound both LDL and apo-E HDLc (apo B,E and apo-E receptors). Furthermore, the membranes from adult human liver revealed the presence of the apo-E receptors as evidenced by the binding of 12--14 ng of HDLc protein per milligram of membrane protein and less than 1 ng of LDL protein per milligram. The membranes from the human liver also bound human chylomicron remnants and a subfraction of human HDL containing apo-E. These data suggest the importance of the E apoprotein and the apo-E receptors in mediating lipoprotein clearance, including chylomicron remnants, by the liver of adult dogs, swine, and man.

Epidermal growth factor receptors.

Abstract: EGF-Rs are cell membrane glycoproteins of wide distribution. They have not yet been fully characterized or purified but are probably molecules of 170-190,000 mol. wt. in most cells. The growth factor EGF binds and will saturate cell surface receptors with a KA of about 5 X 10(9) M-1 although a receptor class with an affinity in excess of 10(10) M-1 has been detected in some cells. The number of receptors on a cell does not determine the level of its response. Some cell types have receptors which bind EGF, but with no mitogenic response. The ways in which receptor affinity and/or number is modulated are described. This and other evidence is reviewed in a search for a suitable model of a mechanism of action on the cell, which best fits the current data. There is ample evidence that EGF binds to the receptor; that ligand-receptor complexes cluster or aggregate; and then are internalized and degraded, but evidence for a direct connection between internalization and the subsequent mitogenic response is lacking. Good correlations between internalization and mitogenic responses have been observed and developed into a theory of endocytic activation, but there is a body of evidence which cannot be accommodated by this theory. Instead, an alternative model is suggested.

Multiple receptor types for octopamine in the locust.

Abstract: 1. Three different pharmacological classes of octopamine receptor mediate the actions of octopamine on the locust extensor-tibiae neuromuscular preparation. A receptor classification scheme is proposed based on the results of detailed studies with agonists and antagonists. 2. Octopamine1 class receptors mediate the slowing of a myogenic rhythm found in a specialized proximal bundle of muscle fibres. Octopamine2A class receptors mediate the increase in amplitude of slow motoneurone twitch tension and octopamine2B class receptors mediate the increase in relaxation rate of twitch tension induced by firing either the fast or the slow motoneurones. 3. Octopamine1 receptors can be distinguished from the 2A and 2B classes since chlorpromazine (and yohimbine) are much better blocking agents than metoclopramide at the former receptors, whereas the converse is true for the latter class. Also clonidine is a more effective agonist than naphazoline for the former receptors and the converse is true for the latter class. 4. Octopamine 2A can be distinguished for octopamine 2B receptors since metoclopramide, mianserin and cyproheptadine show a strong preference for blocking the former class. Also naphazoline is a much better agonist than tolazoline at the former receptors and tolazoline is a much better agonist than clonidine at a latter. 5. The results are discussed in terms of the location of the various classes of octopamine receptors, their possible relationship to vertebrate alpha-adrenoreceptors, and the significance of the results for studies on octopamine receptors in the vertebrate central nervous system.