Showing papers on "Receptor published in 1971"

Insulin--receptor interactions in adipose tissue cells: direct measurement and properties.

Abstract: An assay system is described for measurement of specific binding of [125I]insulin to intact fat cells and membrane fractions from such cells. The binding is time- and temperature-dependent and saturable with respect to insulin; the bound insulin is displaced by native insulin but not by oxidized or reduced insulin or by a number of other peptide hormones. A maximum of about 11,000 molecules of insulin can bind per cell. The insulin-receptor association is a bimolecular reaction with a rate constant of 1.5 × 107 M-1 sec-1, while the dissociation is a strictly first-order process with a rate constant of 7.4 × 10-4 sec-1. A dissociation constant of 5.0 × 10-11 M can be calculated from these rate constants, whereas a value of 6.1 × 10-11 M is obtained on the basis of enhancement of glucose oxidation. Complex formation does not result in chemical change or inactivation of insulin or receptor. The total binding capacity of fat cells is quantitatively recovered in the particulate fraction after homogenization. The insulin-cell receptor interaction is a simple dissociable process involving a homogeneous species probably present exclusively in the cell membrane.

Specific cytoplasmic glucocorticoid hormone receptors in hepatoma tissue culture cells.

Abstract: Kinetic and equilibrium studies are presented for the reversible binding of [(3)H]dexamethasone by "specific" macromolecular receptors in the cytoplasmic fraction of cultured rat hepatoma cells. As in the case of the nuclear receptors in the same cells, the binding affinities of various steroids for the cytoplasmic receptors are closely correlated with the activities of these compounds as inducers of both tyrosine aminotransferase (EC 2.6.1.5) and cell adhesiveness. This suggests that the binding reaction is important for the biological effects of the hormones. Steroid-binding activity is inhibited by various proteases, mercurials, and 1 M KCl, but not by DNase or RNase. The receptors sediment in sucrose gradients in 0.5 M KCl near 4S, and at lower ionic strength near 7S; some of their physical properties are altered upon binding steroid. Bound dexamethasone can be recovered from the receptors as the unaltered steroid.

Glucocorticoid Receptors in Lymphoma Cells in Culture: Relationship to Glucocorticoid Killing Activity

Abstract: Mouse lymphoma cells in culture which are killed by adrenal steroids contain specific cortisol receptors that may be involved in the initial events of hormone action The similarity of these receptors to those in hepatoma tissue culture cells, where adrenal steroids induce tyrosine aminotransferase, suggests that certain aspects of steroid action are similar in the two systems In three steroid-resistant lymphoma cell populations specific binding was less than in the parent lines, suggesting that conversion to steroid resistance may be associated with changes in specific steroid binding

Immunoglobulins as cell receptors.

Abstract: It is conceivable that immunoglobulin molecules in a suitable position on the external membrane of immunocytes may play the role of cell receptors. Through an interaction of these antibody molecules with the corresponding antigens, the cells might be triggered to proliferation and/or differentiation. This might be a crucial role played by membrane-bound immunoglobulins in the immune response, and it is therefore of considerable interest to study the presence, distribution and specificity of immunoglobulin molecules on the membrane of lymphoid cells. The first demonstration of the presence of immunoglobulin determinants on the membrane of lymphocytes has been provided by the blast transformation of these cells after contact with antiimmunoglobulin or antiallotype antisera.' More direct demonstration has been provided by the immunocytoadherence with marker erythrocytes sensitized with immunoglobulins or with radiolabeled antiimmunoglobulin an t ib~dies .~ Recently, a direct visualization of surface immunoglobulins on lymphocyte membrane has been achieved by immunofluorescence.4-8 The purpose of this paper is to report briefly further experiments on the immunoglobulins on the membrane of human or rabbit lymphocytes, and also give a preliminary account of immunoglobulins which are demonstrable on the membrane of some cells of the plasma cell series. Particularly interesting in the latter case is the comparison of the membrane immunoglobulins with the immunoglobulins present in the cytoplasm. These studies have been performed by means of immunofluorescence, utilizing appropriate double-staining procedures in two steps to study the surface and intracytoplasmic immunoglobulins of the same cells, in conjunction with optimal instruments which allow selective visualization of fluorescein or rhodamine.7

Regulation of Adenosine 3′:5′-Cyclic Monophosphate Concentration in Cultured Human Astrocytoma Cells by Catecholamines and Histamine

Abstract: Norepinephrine, epinephrine, and histamine cause a rapid increase in the concentration of adenosine 3′:5′-cyclic monophosphate (cAMP) in a tumor astrocyte cell line derived from a primary culture of a human glioblastoma multiforme. The catecholamine-induced increase in cAMP is dependent on the cell density, being far greater in cells in the log phase of growth than in cells near terminal density. The response to norepinephrine is inhibited 50% by 0.01 μM propranolol, a blocking agent of β-adrenergic receptors. In contrast, the effect of histamine on cAMP concentration varies only slightly from log-phase growth to terminal density, and is not inhibited by 10 μM propranolol. The results suggest that astrocytoma cells have independent receptors for catecholamines and histamine. Further, if the astrocytoma cell is an adequate model of the normal glial cell, these results suggest that astrocytes in human cerebral cortex may be sensitive to norepinephrine and histamine.

Effect of the Androgen-insensitivity Mutation on a Cytoplasmic Receptor for Dihydrotestosterone

Abstract: A mutation which confers insensitivity to androgenic hormones causes a great decrease in the ability of kidney cytoplasmic receptors to bind dihydro-testosterone. This results in a lower nuclear uptake of the steroid.

Oestradiol receptors in carcinoma and benign disease of the breast: an in vitro assay.

Abstract: An assay is described for measuring the concentration of specific, high-affinity oestradiol receptors in the cell supernatant fraction of breast tumour biopsies. The method has been applied to biopsies from 94 patients with malignant and benign diseases of the breast. Of the 53 biopsies classified as carcinomas, 37 contained high-affinity oestradiol receptors in concentrations ranging from 0·3-22·6 × 10-15 moles/mg. tissue, 2 were borderline, and 14 did not contain any receptor. The proportion of positive results and the range of concentrations were found to be somewhat higher in postmenopausal than in premenopausal patients. Despite detailed examination, no histological feature was found which could explain the variation in receptor concentration; neither could it be accounted for by differences in the cellularity of the biopsies. Of the 41 benign breast biopsies examined only 3 contained any high-affinity oestradiol receptor and in these the concentration was very low, ranging from 0·3-0·6 × 10-15 moles/mg. tissue. The receptor has not been detected in normal breast tissue. The relationship between the presence of oestrogen receptors and hormone responsiveness in tumours is discussed.

IgG subclass specificity of human monocyte receptor sites.

Abstract: MONOCYTES as well as macrophages have receptor activity for IgG and the third component of complement1–5. The receptor sites may act independently or cooperatively in binding and ingestion of red cell-antibody complexes2–5. Myeloma proteins of known subclass specificity used as inhibitors of phagocytosis of various red cell–IgG antibody complexes provided suggestive evidence for a subclass specificity of these receptor sites1. We wish to report experiments which define this subclass specificity further and indicate similarities for the binding sites of both γG1 and γG3.

Abnormal hormone responses of an adrenocortical cancer adenyl cyclase.

Abstract: Properties of adenyl cyclase of normal adrenals and of a corticosterone-producing adrenal cancer of the rat have been compared. Enzyme activity was found in all particulate fractions of both tissues. The cyclase of the tumor as well as of the adrenals was stimulated by adrenocorticotropic hormone (ACTH) over similar concentration ranges. Unexpectedly, the tumor enzyme was also stimulated by epinephrine, norepinephrine, and thyroid-stimulating hormone (TSH). These hormones produced a dose-related effect over a concentration span that was comparable with that for ACTH. The tumor cyclase was not responsive to angiotensin Il, vasopressin, glucagon, insulin, growth hormone, parathyroid hormone, and thyrocalcitonin. ACTH was the only hormonal preparation that stimulated normal adrenal cyclase. These findings are compatible either with the possibility that the adenyl cyclase receptor of the tumor has undergone structural alteration with a consequent loss of specificity for ACTH or with the possibility that the tumor possesses several cyclase regulatory receptors.

Receptors on immunocompetent cells : ii. specificity and nature of receptors on dinitrophenylated guinea pig albumin-125i-binding lymphocytes of normal guinea pigs

Abstract: Nonimmunized guinea pigs possess rare lymphocytes which bind sufficient 2,4-dinitrophenyl-guinea pig albumin-125I (DNP-GPA) to their surface to be detected by short-term radioautography. The cells occur in the lymph nodes, spleen, peripheral blood, and bone marrow with a frequency of ∼40/100,000 lymphocytes, but are absent from the thymus. The receptors of these cells are largely specific for the haptenic group (ϵ-DNP-L-lysine) as shown by inhibition of DNP-GPA-125I binding with ϵ-DNP-L-lysine and with DNP bovine serum albumin (DNP-BSA). Furthermore, these cells specifically adsorb to agarose beads to which either DNP-GPA, DNP-BSA, or DNP-keyhole limpet hemocyanin (KLH) has been covalently linked. This hapten specific depletion of DNP-GPA-125I antigen-binding cells (ABC) correlates with a similar diminution in the capacity of adsorbed populations to transfer primary responsiveness to DNP-KLH to irradiated syngeneic recipients. Fluoresceinated anti-immunoglobulin binds to the surface of some guinea pig lymphocytes, and all DNP-GPA-125I ABC, as shown by a double-label technique. The great majority of DNP-GPA ABC and human γ-globulin ABC possess surface Ig molecules of the γ2 heavy chain class. Preincubation of cell suspensions with anti-γ2 antibody markedly diminishes the number of DNP-GPA-125I ABC which are detected, strongly suggesting that the receptors of these cells are immunoglobulin molecules, most of which possess γ2 heavy chains. The specificity characteristics of DNP-GPA-125I ABC are strikingly different from those of cells mediating a cellular immune response to DNP-GPA, indicating major differences in the specificity and nature of the receptors of these cell types.

Studies on a radioligand - receptor assay system for luteinizing hormone and chorionic gonadotropin

Abstract: The binding of 125I-Labelled human luteinizing hormone (LH) and chorionic gonadotropin (HCG) to the interstitial cell fraction of the rat testis has been applied to the development of a radioligand-receptor assay system for gonadotropins.

The action of beta-adrenergic blocking and stimulating agents on insulin secretion. Characterization of the type of beta receptor.

Abstract: As a result of our experiments designed to studyin vivo in the anaesthetized dog, the role of the beta-adrenergic receptors involved in insulin secretion, we have found: 1. that isoprenaline (global stimulator of the beta-adrenergic receptors) provoked a considerable increase in the secretion of insulin. — 2. that propranolol (blocking agent of the beta-adrenergic receptors) partially and temporarily inhibited the secretion of insulin. — 3. that isoprenaline, after blockage of the beta-adrenergic receptors by propranolol, provoked a strong, long-lasting inhibition of insulin secretion. — 4. that practolol (selectivelyβ 1 blocking agent) did not counteract the stimulating effects of isoprenaline (β 1 andβ 2 stimulating agent). This suggests that the beta-adrenergic receptor involved in insulin secretion is of the typeβ 2. — 5. that salbutamol (selectiveβ 2 stimulating agent) provoked an abundant secretion of insulin, an effect which was found to be blocked by propranolol. This last fact confirms that the beta-adrenergic receptor involved in the insulin secretion provoked by isoprenaline is of typeβ 2. — All these findings underline the importance of theβ 2 adrenergic receptors of the beta cell of the islets of Langerhans, in the process of insulin secretion.

Soluble Complexes between Steroid Hormones and Target-Tissue Receptors Bind Specifically to Target-Tissue Chromatin

Abstract: Cytoplasmic fractions containing steroid hormone receptor were prepared from rat prostate and uterine tissues, incubated first with [3H]dihydrotestosterone or [3H]estradiol, and then with their respective target and non-target tissue chromatins. Only prostate and testis chromatin bound the dihydrotestosterone-receptor complex from prostate cytosol extensively. Similarly, uterine chromatin bound more estradiol-receptor complex from uterus than did liver, spleen, or lung chromatin. Complexes between dihydrotestosterone or estradiol with cytosols prepared from liver and spleen bound less extensively, and similarly, to all chromatins. Analogous results are described for the [3H]progesterone-receptor complex from chick oviduct cytosol binding to oviduct chromatin. These studies suggest that the chromatin of all steroid hormone target tissues may contain “acceptor sites” for their respective hormone-receptor complexes, and are thus programmed to receive the complex as it is transferred into the nucleus from the cytoplasm of the cell.

Receptors for C3 on B Lymphocytes: Possible Role in the Immune Response

Abstract: Publisher Summary This chapter discusses the possible role of receptors for C3 on B lymphocytes in the immune response. Complement–receptor lymphocytes (CRLs) have been defined as a population of lymphoid cells found in many mammalian species, including man, which is capable of binding antigen–antibody–complement complexes through a membrane receptor for a modified complement component (C3). CRL can be readily identified and isolated by virtue of their ability to form rosettes with sheep erythrocytes that have been sensitized with rabbit antibody against the Forssmann antigen and complement. CRL have a characteristic distribution in lymphoid organs thatgrossly coincides with that of lymphocytes carrying easily detectable immunoglobulin (Ig) determinants on their membranes. They are absent from the thymus and can be found in large numbers among cells from the lymph nodes, spleen, and thoracic duct lymph of normal mice. The chapter discusses the differences between CRL and mononuclear phagocytes. It also describes the function of the C3 receptor on lymphocytes.

Nature of oestrogen specific binding sites in the nuclei of mouse uteri.

Abstract: IT is widely accepted that the rodent uterus when exposed to oestradiol-17β either in vivo or in vitro interacts with a specific receptor molecule and that this interaction does not involve a chemical transformation of the steroid1,2. Initially, the hormone binds to a protein in the cytoplasm to yield an oestradiol-receptor complex sedimenting in the region of 8S on sucrose gradients3,4. Then, by a temperature dependent process, the bound hormone is transferred to the nucleus where it becomes associated with the chromatin fraction5,6. Therefore, at least one function of oestrogen seems to be to activate the specific cytoplasmic uterine receptor to enter the nucleus and the nature of this nuclear binding is important in elucidating the mechanism of oestrogen action on a molecular basis.

The hepatic chalone. I. Assay method for the hormone and purification of the rabbit liver chalone.

Abstract: Chalone from rabbit liver has been purified 450-fold; it is a polypeptide of small molecular weight. Its action on liver DNA synthesis is tissue-specific but not species-specific. The dose–effect relationship is in agreement with the theory of receptor sites in the hepatocytes with a low affinity for this hormone.

Receptors on immunocompetent cells : iii. specificity and nature of receptors on dinitrophenylated guinea pig albumin-125i-binding cells of immunized guinea pigs

Abstract: Guinea pigs immunized with 2,4-dinitrophenyl-guinea pig albumin (DNP-GPA) possess lymphocytes which specifically bind sufficient DNP-GPA-(125)I to their surface to be detected by radioautography. These lymphocytes are present in the draining lymph nodes in a frequency of approximately 50/1000 lymphocytes in animals immunized 2-4 wk earlier with DNP-GPA in complete Freund's adjuvant. Nonimmunized animals have approximately 0.4 DNP-GPA antigen-binding cells (ABC) per 1000 lymphocytes. An increase in the frequency of DNP-GPA ABC in peripheral blood is detectable by 5 days after immunization, which is before the time that serum anti-DNP antibody is measurable. The receptors of these ABC are hapten specific in that free epsilon-DNP-L-lysine, at low concentration, inhibits the binding of DNP-GPA-(125)I; DNP bovine serum alumbin (DNP-BSA) is equivalent to DNP-GPA in the inhibition of binding of DNP-GPA-(125)I to ABC; and both DNP-GPA agarose beads and DNP-BSA agarose beads specifically adsorb DNP-GPA-(125)I ABC. Anti-immunoglobulin antisera, particularly anti-gamma(2) sera, inhibit the binding of DNP-GPA-(125)I to these cells implying that the receptors are immunoglobulin, primarily of the gamma(2) heavy chain class. DNP-GPA-(125)I ABC appear to represent precursors of antibody-secreting cells and have specificity characteristics which are very different from cells, of similarly immunized guinea pigs, which mediate a cellular immune response to DNP-GPA.

The nature of the colicin k receptor of escherichia coli cullen

Abstract: Cell walls of E. coli strains B and Cullen contain specific receptors for colicin K and for the T2, T6, and C16 phages. The receptors for the bacteriocin and the T6 virus are located in the outer layers of the cell wall of these microorganisms and are absent in their cytoplasmic membrane. The receptors for colicin K, phage T2, and the T6 and C16 viruses differ in their stability toward enzymes and chemical reagents. Their specificity must therefore be determined by different chemical groupings. The colicin K receptor is inactivated by certain proteolytic enzymes and by reagents which combine with tryptophan. It is concluded therefore that proteins or peptides containing this amino acid are essential for biological activity of the receptor.

Simultaneous occurrence of individual estrogen- and androgen receptors in female and male target organs.

Abstract: Reserachers at the Max-Planck-Institut fur Zellbiologie in Wilhelmshaven Germany studied possible relationships between estradiol receptors and dihydrotestosterone receptors in uteri seminal vesicles and prostates. Tissues were removed from 12-week-old calves and 6-month-old castrated male pigs. The dihydrotestosterone receptor remained in solution while the estradiol receptor was removed from target organ extracts by absorption to the coupling product of (4-diazobenzyl) cellulose andestradiol in 2- or 4- position. The 2 receptors are individual but concomitant in the target organs of both sexes. On the other hand a 1000-fold excess of estradiol completely inhibited the binding of dihydrotestosterone to its receptor. A 1000-fold excess of dihydrotestosterone resulted in a 42% reduction of receptor-bound estradiol. Thus although the receptors are individual a cross-affinity also exists. With physiological concentrations the cross-affinity may be of only negligible importance. The beneficial effects of high estrogen doses to prostate cancer patients may be due to competitive inhibition of androgens.

Binding of estradiol-17-beta to human cancer tissue of the female genital tract.

Abstract: Summary We investigated whether tumors of the human female genital tract bind estradiol-17β, i.e. , whether they contain so-called estrogen receptors. Tumor material was obtained from patients who had not received previous irradiation or hormones. In most cases the binding of estradiol-17β in the tumor was related to that in normal vaginal tissue. Twenty-six patients with carcinoma of the uterine cervix were studied. The tumors generally had very low levels of estrogen receptors. In only three cases was the receptor content in the tumors higher than in the corresponding vagina. Nine patients had adenocarcinoma of the endometrium; in these patients, four tumors had a very high receptor content, three tumors had intermediate levels, and, in two tumors, receptors were virtually absent. The very high level in some cases was paralleled by hyperplastic endometrium and was far above the levels of normal endometrium. Receptor content of the endometrial cancers seemed to be related to the histopathology of the tumors; highly differentiated tumors had high levels, while poorly differentiated tumors had low levels. Two metastatic adenocarcinomas (at least one of them of endometrial origin), one leiomyosarcoma of the uterine body, two tumors in the vagina, and one tumor in the vulva virtually lacked estrogen receptors.