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Showing papers on "Receptor published in 1969"


Journal ArticleDOI
TL;DR: It was concluded that the hormones act at discrete hormone-specific sites (or receptors) that affect the activity of a single adenyladenyl cyclase in fat cells.

335 citations


Journal ArticleDOI
TL;DR: Lung irritant receptors have been studied in rabbits by recording action potentials from single vagal nerve fibres and some of the rabbits were bilaterally vagotomized, and some paralysed and artificially ventilated.
Abstract: 1. Lung irritant receptors have been studied in rabbits by recording action potentials from single vagal nerve fibres. Some of the rabbits were bilaterally vagotomized, and some paralysed and artificially ventilated.2. The receptors gave rapidly adapting irregular discharges on inflation and deflation of the lungs. Many were stimulated by insufflation of ammonia vapour into the lungs, and some by passage of a fine catheter into the right bronchial tree. The fibres had conduction velocities in the range 3.6-25.8 m/sec.3. The receptors were strongly stimulated by intravenous injections of histamine acid phosphate, 25-100 mug/kg. The response was considerably reduced by previous injection of isoprenaline which also reduced the bronchoconstriction due to histamine.4. The receptors were stimulated by intravenous injections of isoprenaline, phenyl diguanide and micro-emboli, and by anaphylaxis induced in rabbits previously sensitized to egg albumin.5. The receptor responses could not be closely correlated in size with simultaneous changes in total lung resistance, lung compliance, tidal volume or breathing frequency.6. It is concluded that, in rabbits with intact vagus nerves, lung irritant receptors contribute to the reflex hyperpnoea and bronchoconstriction of the conditions studied.

260 citations


Journal ArticleDOI
TL;DR: Characterization of the still crude receptor fraction showed that it contains significant amounts of RNA and that it may exist in multiple forms, i.e., a 50,000-70,000 and a >200,000 molecular weight species.
Abstract: Evidence has been presented for the existence of an acidic protein(s) or protein portion of a more complex molecule which has a high affinity for binding noncovalently a biologically active metabolite of vitamin D. This molecule could be solubilized from the residual chromatin via treatment with either 0.3 M KCl or high pH and has been purified 167-fold over the crude mucosa homogenate. Characterization of the still crude receptor fraction showed that it contains significant amounts of RNA and that it may exist in multiple forms, i.e., a 50,000-70,000 and a >200,000 molecular weight species. The binding capacity of the receptor fraction for the metabolite is saturated after administration of a physiological dose of the parent vitamin D.

187 citations


Journal Article
TL;DR: The integrity of this receptor was demonstrated on monocytes obtained from patients with `acquired' agammaglobulinaemia, chronic granulomatous disease and acute monocytic leukaemia, and it is proposed that this receptor is an immunological marker for identification of mononuclear cells.
Abstract: Using red cells sensitized with an IgG anti-Rh0 antibody, an IgG receptor was demonstrable on human monocytes, hepatic macrophage and splenic macrophage preparations. The receptor was uniformly lacking on lymphocytes, lymphoid cell lines and lymphocytes stimulated with phytomitogens in vitro. The integrity of this receptor was demonstrated on monocytes obtained from patients with `acquired' agammaglobulinaemia, chronic granulomatous disease and acute monocytic leukaemia. There was no direct correlation between the presence of the receptor and the fine structure of the cells studied. It is proposed that this receptor is an immunological marker for identification of mononuclear cells.

186 citations


Journal ArticleDOI
TL;DR: It is postulated that the catecholamine release which is stimulated by volume depletion, infection, or stress may be an important "reversible" factor in some patients with diabetic ketoacidosis.
Abstract: This review summarizes evidence showing inhibition of insulin release by epinephrine and norepinephrine. The receptor theory for catecholamine action is discussed and the inhibition shown to be mediated by α-adrenergic receptor stimulation; β-adrenergic receptors are also described which stimulate insulin release, indicating a unique dual receptor system in the pancreatic islet. The possible physiologic importance of these findings is suggested in a discussion of the carbohydrate intolerance found in patients with pheochromocytoma and during severe hypothermia in children. A possible relation of the inhibition of insulin release and the increased fatty acid mobilization caused by catecholamines to exacerbations of the diabetic syndrome is examined. It is postulated that the catecholamine release which is stimulated by volume depletion, infection, or stress may be an important "reversible" factor in some patients with diabetic ketoacidosis.

142 citations


Journal Article
TL;DR: Mouse leukocytes have distinct membrane receptor sites for sheep red blood cells sensitized with either the 7 S or the 19 S fractions of a mouse anti-SRBC antiserum, which distinguishes them from the receptors for complement component(s) present on the same cells.
Abstract: Mouse leukocytes have distinct membrane receptor sites for sheep red blood cells (SRBC) sensitized with either the 7 S (EA (7S)) or the 19 S (EA (19 S)) fractions of a mouse anti-SRBC antiserum. The receptors for EA (7 S) or EA (19 S) can be distinguished from each other because the binding of EA (7 S) to macrophages is inhibited by normal 7 S mouse immunoglobulins, whereas the binding of EA (19 S) is unaffected. Moreover, the binding of EA (19 S) to macrophages depends on the presence of Ca++ ions in the incubation medium while EA (7 S) adheres to leukocytes in the presence of Na3HEDTA. The receptors for EA (7 S) were found on macrophages, blood monocytes and polymorphonuclear leukocytes, while the receptors for EA (19 S) were detected only on macrophages. The receptors for both 7 S and 19 S immunoglobulins are not destroyed by trypsin treatment of the macrophages, and this property distinguishes them from the receptors for complement component(s) present on the same cells (2).

104 citations



Journal Article
TL;DR: It is postulated that agonists cause a change in the molecular structure of the receptor that increases the affinity of the receptors for certain antagonists, and this molecular change may be related to the processes of stimulation and desensitization by agonists.
Abstract: The effects of various curare-like compounds on the contractile responses to carbachol and suxamethonium of thin strips of chick biventer cervicis and of leech muscle have been studied. In chick muscle, suxamethonium and carbachol appeared to act on the same receptor, and were antagonized by tubocurarine, gallamine, and three substituted decamethonium derivatives. The actions of tubocurarine and gallamine, deviated only very slightly from the conventional competitive model; in contrast, the decamethonium derivatives exhibited a qualitatively different kind of antagonism. Experiments with these compounds, including a 2-chloroethylamine derivative that caused an irreversible type of block, showed that the degree of antagonism produced was increased if the antagonist was applied at the same time as, or shortly after, a dose of agonist. This was confirmed in experiments with leech muscle, in which suxamethonium and carbachol appeared to act on different receptors; the substitute decamethonium compounds showed specificity for the suxamethonium receptors, and here the same kind of interaction with agonist as had been seen with chick muscle was observed. It is postulated that agonists cause a change in the molecular structure of the receptor that increases the affinity of the receptor for certain antagonists. This has been termed the metaphilic effect, and it is suggested that this molecular change may be related to the processes of stimulation and desensitization by agonists.

76 citations


Journal ArticleDOI
Y.H. Abdulla1
TL;DR: Evidence is presented for the existence of β-adrenergic receptors effecting disaggregation of clumped platelets and this function is mediated by adenosine 3′-5′ cyclic monophosphate.

62 citations


Journal ArticleDOI
TL;DR: The distribution and rate of appearance of newly synthesized receptors on the surface of Burkitt lymphoma cells were determined by membrane immunofluorescence tests on trypsinized cell lines growing as continuous cultures in a medium containing gamma globulins with specificity for the receptors.
Abstract: The distribution and rate of appearance of newly synthesized receptors on the surface of Burkitt lymphoma cells were determined by membrane immunofluorescence tests on trypsinized cell lines growing as continuous cultures in a medium containing gamma globulins with specificity for the receptors. An attempt was made to determine the fate of the „surface receptor-serum globulin” complex by examining serial samples of cultures of stained positive cells for membrane immunofluorescence. There is partial evidence to suggest that observed fluctuations in the numbers of receptor-producing cells are partly due to active shedding of receptors from the cell surfaces.

55 citations



Journal ArticleDOI
TL;DR: Different estrogen derivatives have been studied and there is some correlation between their affinity for limited capacity receptors and their uterotrophic activity, but with acoefficient smaller than that of the uterus.
Abstract: Interaction of estradiol with rat uterus “receptors” has been studied using tissue incubation. The reversibility of estradiol binding has been confirmed and 2 types of binders have been observed. The first have great affinity, limited capacity and high specificity. The other, having smaller affinity and nonlimited capacity in the range of concentration used (up to 1 × 10-5 M), can be treated as a “partition” system. Nontarget organs, such as muscle or fat, also incorporate estradiol as a partition system, but with acoefficient smaller than that of the uterus. Different estrogen derivatives have been studied and there is some correlation between their affinity for limited capacity receptors and their uterotrophic activity. After incubation at 37 C, there is no “8 S” cytoplasmic estrogen binder, whereas there is more estradiol incorporated into nuclei than after 2 C incubation when the “8 S receptor” is preserved. (Endocrinology 84: 108, 1969)

Journal ArticleDOI
TL;DR: It is concluded that the antigen receptor on the sensitized lymph node cell differs in both kind and degree from conventional antibody, and the chemical nature of the receptor and the means by which this receptor reacts with antigen to initiate the biosynthetic or proliferative cellular immune response still remain undefined.
Abstract: Studies of the immunochemical specificity of antigen-induced thymidine-2-(14)C incorporation in lymph node cells obtained from animals immunized to a series of closely related alpha-DNP-oligolysines, epsilon-DNP-oligolysines, and oligolysines have shown that the sensitized cell exhibits an extraordinary degree of specificity for antigen. The sensitized cell is maximally stimulated by the homologous immunizing antigen and can discriminate among compounds which differ from one another only in the position of a dinitrophenyl group or D-lysine residue on an identical oligolysine backbone. These studies support the view that the immunogen is not degraded prior to the induction of the immune response, and that the majority of cells produced as a consequence of immunization have stereospecific antigen receptors for the DNP-oligolysine used to induce the response; a smaller and more variably sized population of cells is produced with receptors specific for the oligolysine portion of the immunizing antigen. When specifically sensitized lymph node cell cultures are stimulated in vitro by heterologous DNP-oligolysines, the oligolysine- and not the DNP-oligolysine-sensitive population of cells appears to play a crucial role in the specificity of such cross-reactions. It is concluded from these studies that the antigen receptor on the sensitized lymph node cell differs in both kind and degree from conventional antibody. The chemical nature of the receptor and the means by which this receptor reacts with antigen to initiate the biosynthetic or proliferative cellular immune response still remain undefined.

Journal ArticleDOI
27 Sep 1969-Nature
TL;DR: The idea that antibody-like molecules are present on the membrane of the lymphoid cell is supported by observations that antibodies to immunoglobulins induce transformation in lymphoid cells3.
Abstract: INDUCTION of an antibody response is thought to involve an initial phase of antigen recognition by cells, but it is not yet known whether the recognizing cell is the precursor of the antibody producing cell or a distinct antigen sensitive cell1. In any case, recognition is believed to take place through a cell-surface receptor. This was suggested from experiments in which free haptens inhibited the immunogenic effect of hapten–protein conjugates. Furthermore, closely related haptens interfered with the response induced by the hapten–protein conjugate; the antibodies inhibited were those which cross-reacted with the related haptenic determinant2. Studies to characterize such a cell receptor indicated that antibodies inhibit induction of a response, possibly by competing with the receptor for the antigen2, which suggested that the receptor is an antibody-like entity. The idea that antibody-like molecules are present on the membrane of the lymphoid cell is supported by observations that antibodies to immunoglobulins induce transformation in lymphoid cells3.

Journal ArticleDOI
15 Feb 1969-Nature
TL;DR: Stimulation of nucleic acid synthesis in vitro by specific anti-H-chain sera was used as a criterion for the presence of receptors with μ or γ-chain specificity on lymphocytes to investigate the phenotypic expression of H-chain controlling genes in lymphocytes.
Abstract: THERE is currently a great deal of interest in binding sites (receptors) on lymphocytes with respect to their role: (a) for recognition of antigens, (b) as “trigger sites” for lymphocyte differentiation and proliferation, (c) as markers of the type and specificity of antibodies that the progeny of the cell will produce if stimulated, and (d) in regulating whether immunity or tolerance is induced by exposure to the antigen1–3. The well defined antigenic structure of immunoglobulins makes it possible to look for the presence of immunoglobulin-type receptors using anti-immuno-globulin sera. The interaction of anti-immunoglobulin antibodies with small lymphocytes in cell culture stimulates nucleic acid synthesis and the transformation of lymphocytes to blast cells5. We have used this approach to investigate the phenotypic expression of H-chain controlling genes in lymphocytes. Stimulation of nucleic acid synthesis in vitro by specific anti-H-chain sera was used as a criterion for the presence of receptors with μ or γ-chain specificity on lymphocytes.

Journal ArticleDOI
TL;DR: The mercury derivative can be used for identification of target organ receptor proteins and study of their role in the mechanism of estrogen action and is demonstrated to mimics 17β-estradiol in the production of several biological responses and in the nature of its binding to soluble uterine receptor sites.

Journal ArticleDOI
TL;DR: The administration of glucose, tolbutamide, corticotropin, and glucagon to mice resulted in stimulation of insulin secretion and the locus of the inhibitory effects of β-adrenergic receptor blocking agents on insulin secretion is discussed.
Abstract: The administration of glucose, tolbutamide, corticotropin, and glucagon to mice resulted in stimulation of insulin secretion. These stimulations were all inhibited by the prior administration of β-adrenergic receptor blocking agents. Cyclic 3',5' adenosine monophosphate stimulated insulin secretion in intact mice and its stimulatory effect was also inhibited by β-adrenergic receptor blocking agents. The locus of the inhibitory effects of β-adrenergic receptor blocking agents on insulin secretion is discussed.


Journal Article
TL;DR: Subdivision of pseudocholinesterase of rat atrium on the basis of cellular localization and function was suggested, suggesting functional —SH groups at the receptor active sites at atrial cholinergic receptors.
Abstract: Pacemaker cells were more highly selective in cholinergic agonist requirements than contractile cells since rate was essentially unaffected by choline, butyrylcholine and long-chain choline esters that definitely depressed amplitude. Acetylcholine depressed rate and amplitude to about the same extent and was the most potent choline ester of the series. Choline esters of the same chain length as acetylcholine were about 10 times less potent. Cholinergic receptors of pacemaker cells appeared to be surrounded by denser cholinesterase activity than cholinergic receptors of contractile cells, since inhibition of cholinesterase produced profound potentiation of acetylcholine depression of rate and only moderate potentiation of acetylcholine depression of amplitude. Cholinesterase inhibition markedly potentiated the action of acetyl-β-methylcholine and propionylcholine but did not potentiate butyryl choline action. Hence, pseudocholinesterase which hydrolyzes butyryicholine may not be able to modify agonist action at atrial cholinergic receptors, although true acetylcholinesterase and pseudocholinesterase which hydrolyzes propionylcholine can modify agonist action. Thus, subdivision of pseudocholinesterase of rat atrium on the basis of cellular localization and function was suggested. Cholinesterase inhibitors, except di-isopropyl fluorophosphate, at low concentration potentiated agonist action but at high concentration blocked agonist action, the block on cholinergic receptors of pacemaker cells being more intense than on receptors of contractile cells. Pacemaker cell cholinergic receptors were more readily blocked by atropine than contractile cell receptors. Pacemaker cell cholinergic receptors were rapidly and intensely blocked by N-ethylmaleimide, suggesting functional —SH groups at the receptor active sites. N-ethylmaleimide produced a slowly developing, weaker block of contractile cell cholinergic receptors.

Journal ArticleDOI
24 May 1969-Nature
TL;DR: It is easily shown that the action of the fast antagonist can be described by the relation where ybc/yb is the fraction of receptors occupied by the agonist in the presence of both slow (b) and fast (c) antagonists, and the addition of thefast antagonist will be expected to increase the response to a standard dose of agonist.
Abstract: IF drugs b and c are competitive antagonists of drug a, then it would seem self evident that the addition of c to a system in which b was already present would increase the degree of block. But where the receptors are exposed to the agonist for only a short time there is another possibility. If the first antagonist dissociates from the receptors slowly, and the second rapidly, the additional presence of the second antagonist may increase the number of receptors effectively available to the agonist. If, for simplicity, it is supposed that equilibrium between receptors and both the agonist and the “fast” antagonist is instantaneous and that the dissociation rate of the “slow” antagonist is so small that no dissociation occurs during the period of exposure to the agonist, then it is easily shown that the action of the fast antagonist can be described by the relation where ybc is the fraction of receptors occupied by the agonist in the presence of both slow (b) and fast (c) antagonists, yb the fraction occupied by the agonist in the presence of only b, X is the fraction of receptors which would have been occupied by c, Y by the agonist and Z by b at equilibrium if each of the substances had been present alone. Evidently, if ybc/yb is greater than 1, the addition of the fast antagonist will be expected to increase the response to a standard dose of agonist. Fig. 1 shows how ybc/yb varies with X and Z for two different values of Y. For the larger value of Y the paradoxical effect is observed for a range of values of X and Z; for the smaller value of Y, only additional block is seen. In general, ybc/yb cannot be greater than 1 if Y+Z < 1.

Book ChapterDOI
TL;DR: This chapter discusses the preliminary characterization of an estrogen-binding protein from the rat uterus and a theoretical model of its mechanism of amplification, which involves a conformational transition of the protein due to estrogen, which permits the protein to move into or on the nucleus.
Abstract: Publisher Summary This chapter discusses the preliminary characterization of an estrogen-binding protein from the rat uterus and a theoretical model of its mechanism of amplification. The initial sensory or detection system in the uterus is the estrogen-binding site on the cytosol receptor protein. This site is analogous to the allosteric or feedback control site in aspartate transcarbamylase. The amplification system involves a conformational transition of the protein due to estrogen-binding, which, in turn, permits the protein to move into or on the nucleus. Once this protein is in the nucleus, it might regulate gene expression at any of a number of sites ranging from a direct interaction with DNA to control of nuclear membrane transfer of RNA to the cytoplasm. The complex events that must be involved in gene expression and nuclear function in animal cells are difficult to visualize as being responsible for some of the cellular responses that occur within minutes after estrogen administration.

Journal ArticleDOI
TL;DR: The results with the isolated perfused frog heart have disclosed theβ-2 receptor type in this organ, and a review of the available literature suggests that in this species there is also another receptor which resembles the β-1 type.

Journal ArticleDOI
Steven Price1
22 Feb 1969-Nature
TL;DR: A sugar-complexing protein fraction found in homogenates of bovine tongue epithelium suggested that it contained the chemoreceptor molecule for sweet-tasting compounds, which is characterized as a cationic protein of high molecular weight.
Abstract: DASTOLI and I reported earlier that we had found a sugar-complexing protein fraction in homogenates of bovine tongue epithelium1. Because the interaction of this fraction with sugars resembled in several respects the interactions of taste receptors in vivo, we suggested that it contained the chemoreceptor molecule for sweet-tasting compounds. The active component was subsequently purified and was characterized as a cationic protein of high molecular weight2.

Journal Article
TL;DR: It is concluded that when taenia coli is stimulated by increased concentrations of extracellular potassium, alpha receptor activation leads to relaxation by a suppression of the spike activity of the cell membrane; beta receptoractivation leads to Relaxation by an effectnot involving the electrical activity ofThe membrane.
Abstract: The effects of catecholamines on isolated taenia coli from guinea pigs were studied with strain gauge and sucrose gap techniques. Elevated concentrations of potassium (35 and 90 mM) were used to stimulate the smooth muscle. In the presence of 35 mM K + , norepinephrine and epinephrine inhibited spike activity and relaxed the muscle by acting mainly on alpha receptors. A beta receptor component in the relaxation induced by norepinephrine or epinephrine could be demonstrated only when higher concentrations of the agonists were used after blockade of the alpha receptors. Isoproterenol in low concentrations elicited relaxation by beta receptor stimulation, although at higher concentrations relaxation was mediated by alpha receptor stimulation. Relaxation elicited by the lower concentrations of isoproterenol had no effect on the electrical activity. In the presence of 90 mM K + , all three catecholamines caused relaxation through stimulation of beta receptors only. There were no changes in the electrical activity accompanying the relaxation. No alpha receptor- mediated effects on electrical or mechanical activity could be demonstrated in the depolarized taenia. In contrast to the catecholamines, aminophylline elicited relaxation of the taenia in both 35 and 90 mM K + and was not blocked by catecholamine antagonists. We conclude that when taenia coli is stimulated by increased concentrations of extracellular potassium, alpha receptor activation leads to relaxation by a suppression of the spike activity of the cell membrane; beta receptor activation leads to relaxation by an effectnot involving the electrical activity of the membrane.

Journal ArticleDOI
TL;DR: It is proposed that on combination with reduced glutathione the tertiary (or quarternary) structure of the receptor is reversibly converted from an inactive form.

Journal ArticleDOI
30 Aug 1969-Nature
TL;DR: The conditions of antibody inhibition of this in vitro response to sheep red blood cells (SRC) are investigated to understand better the role of antigen in antibody stimulation.
Abstract: THE immune response can be inhibited by passive administration of specific antibody1 It is generally assumed that the antibody, presumably by covering the antigenic determinants of the antigen, prevents the interaction of antigen with the receptors on the target cells The immune response to sheep red blood cells (SRC) can be studied in vitro with Mishell and Dutton's2 technique We have investigated the conditions of antibody inhibition of this in vitro response to understand better the role of antigen in antibody stimulation

Journal ArticleDOI
TL;DR: Dissociation of 3H-estradiol, previously bound to a uterine nuclear receptor by in vitro techniques, was enhanced when incubated with unlabeled estradiol and the distribution of radioactivityradioactivity among cellular fractions was altered.
Abstract: Dissociation of 3H-estradiol, previously bound to a uterine nuclear receptor by in vitro techniques, was enhanced when incubated with unlabeled estradiol. Other estrogens increased dissociation but testosterone produced no effect. Significant differences were noted between the association and dissociation process. Uteri containing 3H-estradiol bound to receptors in vivo were homogenized and incubated under different conditions. The distribution of radioactivityradioactivity among cellular fractions was altered. An increase in nuclear-bound material occurred during incubation at 25 or 37 C, but no change was observed at 4 C. This increase required the supernatant fraction and was specific for estradiol. Similar experiments were performed using 3H-estriol and a comparison between the 2 estrogens is made. (Endocrinology 84: 718, 1969)

Book ChapterDOI
01 Jan 1969
TL;DR: The study of immunity reactions is not only important in itself but it furthers comprehension of other host-environment interactions including those of toxins, drugs or even live agents such as viruses.
Abstract: Immunity reactions are interactions between the host and his environment. In this interaction “receptors” in the sense of Paul Ehrlich (1901) play a paramount role. The study of immunity reactions is not only important in itself but it furthers comprehension of other host-environment interactions including those of toxins, drugs or even live agents such as viruses. In all instances the agent or its products, be they noxious or beneficial, have first to attach to a receptor before they can begin to exert their influence.

Journal ArticleDOI
TL;DR: It was concluded that if brain hormone receptors exist, they do not respond to estradiol as do uterine receptors, and showed a pattern of uptake similar to muscle, a nontarget tissue.
Abstract: Various investigators have postulated that estrogen-sensitive structures contain “receptors” which accumulate and bind estradiol. Further, it has been implied that brain receptors function in a similar way to uterine receptors, even though the evidence for this conclusion is not strong. The present study was designed to compare the accumulation of radioactivity by brain and uterus following 3H-estradiol treatment in estrous, diestrous, and ovariectomized rats. Uterus exhibited high levels of radioactivity in diestrus, but not in estrus or the ovariectomized condition. The accumulation of hormone by brain did not fluctuate with the various levels of endogenous hormone stimulation, but rather showed a pattern of uptake similar to muscle, a nontarget tissue. It was concluded that if brain hormone receptors exist, they do not respond to estradiol as do uterine receptors.

Journal Article
TL;DR: Precipitating antibodies were prepared against the determinant phenoxycholine, a nicotinic agonist, and the affinity of the antibody for a wide range of agonists and antagonists related to acetylcholine was tested.
Abstract: Precipitating antibodies were prepared against the determinant phenoxycholine, a nicotinic agonist. The affinity of the antibody for a wide range of agonists and antagonists related to acetylcholine was tested. The affinity constants were found to range between 3.2 x 105 and 6.9 x 103 M-1. The antibody did not discriminate between agonists and antagonists, or between drugs acting at muscarinic and nicotinic receptors.