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1.
Tick histamine-binding proteins (HBPs) are lipocalins with two binding pockets. One of these binds histamine with a high affinity and is found at the position expected from other lipocalins, adjacent to the omega-loop at the open-end of the beta-barrel. A second binding cavity, which is a low-affinity site for histamine in one of the HBPs, is located at the end of the barrel that is closed off in other lipocalins. In order to create the second site, the 'closed-end' region has undergone a major reconstruction. Typical lipocalin characteristics, such as the 3(10) helix and a structural cluster of highly conserved residues, have been lost, while an alpha-helix now shields the cavity from the exterior. The prominence of acidic residues in the binding pockets is another distinctive characteristic of HBPs. Whereas most lipocalins have highly hydrophobic binding cavities designed to bind lipophilic compounds, HBPs have evolved to trap cationic, hydrophilic molecules. 相似文献
2.
Skeletal diseases have a major impact on the worldwide population and economy. Although several therapeutic agents and treatments are available for addressing bone diseases, they are not being fully utilized because of their uptake in nontargeted sites and related side effects. Active targeting with controlled delivery is an ideal approach for treatment of such diseases. Because bisphosphonates are known to have high affinity to bone and are being widely used in treatment of osteoporosis, they are well-suited for drug targeting to bone. In this study, a targeted delivery of therapeutic agent to resorption sites and wound healing sites of bone was explored. Toward this goal, bifunctional hydrazine-bisphosphonates (HBPs), with spacers of various lengths, were synthesized and studied for their enhanced affinity to bone. Crystal growth inhibition studies showed that these HBPs have high affinity to hydroxyapatite, and HBPs with shorter spacers bind more strongly than alendronate to hydroxyapatite. The HBPs did not affect proliferation of MC3T3-E1 preosteoblasts, did not induce apoptosis, and were not cytotoxic at the concentration range tested (10(-6)-10(-4) M). Furthermore, drugs can be linked to the HBPs through a hydrazone linkage that is cleavable at the low pH of bone resorption and wound healing sites, leading to release of the drug. This was demonstrated using hydroxyapatite as a model material of bone and 4-nitrobenzaldehyde as a model drug. This study suggests that these HBPs could be used for targeted delivery of therapeutic agents to bone. 相似文献
3.
Heparin binds to bovine sperm and stimulates capacitation in vitro. Seminal plasma alters the ability of epididymal sperm to bind heparin, and several heparin-binding proteins (HBPs) have been identified in bull seminal plasma. This study had three objectives: 1) to identify production sites of seminal plasma HBPs, 2) to determine which HBPs bound to cauda epididymal sperm, and 3) to determine whether presence of HBPs was testosterone dependent. Proteins from bull or rat seminal vesicles, prostates, and bulbourethral glands were separated by heparin affinity high-performance liquid chromatography. HBPs were found in all accessory glands of rats and bulls, but the major source of bovine seminal plasma HBPs appeared to be seminal vesicles. Between 25% and 50% of the protein from each gland bound to the heparin column, and NaCl concentrations required to elute proteins ranged from 0.15 to 1.4 M. One-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that major HBPs were relatively small, with molecular weights between 13 and 31 kDa, but some HBPs also exhibited higher molecular weights, between 40 and 100 kDa. Radioiodinated HBPs from each bovine gland were incubated with epididymal sperm. Labeled HBPs binding to sperm exhibited molecular weights of 14, 16, 24, and 30 kDa as determined by SDS-PAGE and autoradiography. The HBP content of the accessory sex glands decreased significantly in castrated rats and was restored to levels of sham-operated controls by testosterone replacement. Heparin-binding proteins may play a role in fertilization by attaching to sperm surfaces, enabling heparin-like glycosaminoglycans in the female reproductive tract to induce capacitation. 相似文献
4.
Effects of phospholipase A2 on numbers of histamine H1 receptors and muscarinic acetylcholine receptors were estimated in guinea pig lungs. Histamine H1 and muscarinic acetylcholine receptors in lung membranes were studied by the direct binding technique using 3H-pyrilamine and 3H-quinuclidinyl benzilate, respectively. The control group had two orders (high-affinity and low-affinity) of binding sites of histamine H1 receptors. Pretreatment of lung membranes with phospholipase A2 destroyed high-affinity binding sites, and these sites could not be detected after treatment. Low-affinity sites were not affected by the treatment. In contrast, the numbers of muscarinic acetylcholine receptors did not change significantly in spite of the addition of phospholipase A2. These results indicate that resistance of receptors against phospholipase A2 treatment varies among receptors and even between the binding sites in the same receptor. These variations might modulate pathological conditions associated with inflammation in which phospholipase is activated. Easy establishment of histamine tachyphylaxis might be explained by this mechanism. 相似文献
5.
de Castro Côrtes LM de Souza Pereira MC de Oliveira FO Corte-Real S da Silva FS Pereira BA de Fátima Madeira M de Moraes MT Brazil RP Alves CR 《Parasitology》2012,139(2):200-207
Leishmaniasis is a vector-borne disease and an important public health issue. Glycosaminoglycan ligands in Leishmania parasites are potential targets for new strategies to control this disease. We report the subcellular distribution of heparin-binding proteins (HBPs) in Leishmania (Viannia) braziliensis and specific biochemical characteristics of L. (V.) braziliensis HBPs. Promastigotes were fractionated, and flagella and membrane samples were applied to HiTrap Heparin affinity chromatography columns. Heparin-bound fractions from flagella and membrane samples were designated HBP Ff and HBP Mf, respectively. Fraction HBP Ff presented a higher concentration of HBPs relative to HBP Mf, and SDS-PAGE analyses showed 2 major protein bands in both fractions (65 and 55 kDa). The 65 kDa band showed gelatinolytic activity and was sensitive to inhibition by 1,10-phenanthroline. The localization of HBPs on the promastigote surfaces was confirmed using surface plasmon resonance (SPR) biosensor analysis by binding the parasites to a heparin-coated sensor chip; that was inhibited in a dose-dependent manner by pre-incubating the parasites with variable concentrations of heparin, thus indicating distinct heparin-binding capacities for the two fractions. In conclusion, protein fractions isolated from either the flagella or membranes of L. (V.) braziliensis promastigotes have characteristics of metallo-proteinases and are able to bind to glycosaminoglycans. 相似文献
6.
L J Brandes W A Beecroft G R Hogg 《Biochemical and biophysical research communications》1991,179(3):1297-1304
We have implicated histamine as a mediator of proliferation through its binding to novel intracellular receptors (HIC), closely associated with antiestrogen binding sites (AEBS) in microsomes and nuclei. N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE), is a potent ligand for AEBS/HIC. We now demonstrate that DPPE stimulates in vivo tumor growth (DMBA-induced mammary cancer in Sprague-Dawley rats and L5178Y leukemia in DBA/2 mice) and synergizes with phorbol-12-myristate-13-acetate (PMA) to induce inflammation and mitotic activity in mouse epidermis. Thus, ligands for intracellular histamine receptors may represent a new class of tumor promoting agents; this finding lends new credence to an important role for histamine in growth. 相似文献
7.
N. Subramanian W. L. Whitmore F. J. Seidler T. A. Slotkin 《Journal of neurochemistry》1981,36(3):1137-1141
The ontogeny of histaminergic neurotransmission in the rat brain was studied by assessing development of histamine levels in brain regions, along with H-1 receptor binding of [3H]mepyramine and H-1 receptor-mediated cellular events. In the hypothalamus, which is rich in histaminergic innervation, levels of the amine were low at birth, increased sharply at 8 days of age, and reached adult concentrations shortly thereafter; this pattern is typical of most neurotransmitters. In contrast, regions poor in neuronal histamine showed an initially high histamine level and a subsequent decline with development, as is known to occur during general growth of tissues. The developmental profile of H-1 receptor binding sites resembled that of the neuronal histamine pool, and the increases with age resulted from changes in the number of binding sites without alterations in Kd. Cellular responses to H-1 receptor activation were assessed by determining the stimulation of phospholipid turnover evoked by intracisternally administered histamine, a process that has been shown to involve only the neuronal compartment. Again, the developmental profile was superimposable upon that of H-1 receptor binding and that of hypothalamic histamine levels. These studies indicate that ontogeny of histaminergic neurotransmission is a coordinated process, with simultaneous development of neuronal histamine, its key biosynthetic enzyme, and H-1 receptors coupled directly to cellular events. 相似文献
8.
Histamine receptors of the microvascular endothelium revealed in situ with a histamine-ferritin conjugate: characteristic high-affinity binding sites in venules 总被引:9,自引:1,他引:8
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《The Journal of cell biology》1982,93(2):357-364
Histamine covalently bound to glutaraldehyde-activated ferritin was prepared as either monomers or as small aggregates of approximately 0.05 to 0.15 micrometer Diam, suitable for electron microscopic detection of histamine cellular binding sites. The histamine-ferritin conjugates (MF) maintain the histamine capability to induce the opening of endothelial junctions in venules. To investigate the distribution of histamine receptors in the vascular endothelium, monomers or aggregates of MF were perfused in situ (mice), and various vascular beds, particularly that of the diaphragm, were fixed and processed for electron microscopy. The conjugate was preferentially bound on restricted areas of luminal endothelial cell plasmalemma especially in regions rich in filaments, and near the junctions between endothelial cells. The density of histamine binding sites was characteristically high in venules; it occurred to a much lesser extent in arterioles, veins, and muscular arteries whereas capillaries and aorta showed the lowest values. A similar distribution was obtained after perfusion of H1 or H2 receptor agonists coupled to ferritin (2-pyridylethylamine- ferritin [PF], or 4-methylhistamine-ferritin [MF], respectively). The binding specificity was assessed through control experiments with either native or activated ferritin or by competition with histamine. The findings suggest that histamine receptors are largely represented in the cell membrane of the vascular endothelium, particularly in venules. Experiments using specific H1 and H2 receptor agonists (PF and MF) and antagonists (mepyramine and cimetidine) indicate that the venular endothelium contains mainly H2 receptors. 相似文献
9.
Kumar V Hassan MI Kashav T Singh TP Yadav S 《Molecular reproduction and development》2008,75(12):1767-1774
Human seminal plasma (HuSP) contains several proteins that bind heparin and related glycosaminoglycans. Heparin binding proteins (HBPs) from seminal plasma have been shown to participate in modulation of capacitation or acrosome reaction and thus have been correlated with fertility in some species. However, these have not been studied in detail in human. The objective of this study was to purify major HBPs from HuSP in order to characterize these proteins. HBPs were isolated by affinity-chromatography on Heparin-Sepharose column, purified by reverse-phase high-performance liquid chromatography (RP-HPLC) and Size-exclusion chromatography and checked for purity on sodium-dodecyl PAGE (SDS-PAGE). Identification of HBPs was done by matrix-assisted laser desorption-ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). Here we report the purification and identification of seven HBPs in seminal fluid. The major HBPs are lactoferrin and its fragments, semenogelin I fragments, semenogelin II, prostate specific antigen, homolog of bovine seminal plasma-proteins (BSP), zinc finger protein (Znf 169) and fibronectin fragments. In this study we are reporting for the first time the purification and identification of BSP-homolog and Znf 169 from HuSP and classified them as HBPs. Here we report the purification of seven clinically important proteins from human seminal fluid through heparin affinity chromatography and RP-HPLC, in limited steps with higher yield. 相似文献
10.
Possible role of histamine in brain function: neurochemical, physiological, and pharmacological indications 总被引:1,自引:0,他引:1
I M Mazurkiewicz-Kwilecki 《Canadian journal of physiology and pharmacology》1984,62(6):709-714
Recently accumulated neurochemical, physiological, and pharmacological evidence strongly supports a role for histamine as a central neurotransmitter. Neurochemical methods, which became available within the last years, allow determination of small amounts of histamine and its metabolites in the brain and make possible future studies of central histamine regulation. The demonstration of histamine H1 and H2 receptors in the brain of several species suggests a possible role for histamine in brain function. Microelectrophysiological studies on single central neurones suggest both excitatory and depressant effects of histamine which are receptor mediated. In addition, brain histamine has been demonstrated to be subject to cyclic variations, to play a role in hormonal regulation, and to be altered by stressful conditions. Several psychotropic drugs significantly affect brain histamine regulation and elicit inhibitory effects on central histamine receptors. These findings bring new approaches and stimulus to further research on the significance of brain histamine. 相似文献
11.
Antinociceptive activity of impentamine, a histamine congener, after CNS administration 总被引:1,自引:0,他引:1
The brain neuromodulator histamine induces antinociception when administered directly into the rodent CNS. However, several compounds derived from H2 and H3 antagonists also produce antinociception after central administration. Pharmacological studies have shown that a prototype of these agents, improgan, induces analgesia that is not mediated by actions on known histamine receptors. Presently, the antinociceptive properties of a compound that chemically resembles both improgan and histamine were investigated in rats. Intraventricular (i.v.t.) administration of impentamine (4-imidazolylpentylamine) induced reversible, near-maximal antinociception on the hot plate and tail flick tests (15 microg, 98 nmol). The dose-response function was extremely steep, however, since other doses showed either no effect or behavioral toxicity. On the tail flick test, impentamine antinociception was resistant to antagonism by blockers of H1, H2, or H3 receptors, similar to characteristics previously found for improgan. In contrast, histamine antinociception was highly attenuated by H1 and H2 antagonists. These findings suggest that: 1) the histamine congener impentamine may induce antinociception by a mechanism similar to that produced by improgan, and 2) additional histamine receptors may be discovered that are linked to pain-attenuating processes. 相似文献
12.
J C Foreman A K Sobotka L M Lichtenstein 《Journal of immunology (Baltimore, Md. : 1950)》1979,123(1):153-159
Strontium will substitute for calcium in the activation of histamine secretion from human basophil leukocytes stimulated by an immunologic reaction or by the ionophore A23187. Strontium is required in 10-fold higher concentration (1 to 10 mM) to activate histamine release compared with calcium (0.1 to 1.0 mM). In terms of maximum release obtainable for a particular immunologic stimulus, strontium is more effective than calcium. Results are presented to show that calcium and strontium act at the same site but strontium is a more sensitive probe for that site. Strontium can be used to demonstrate that immunologic stimuli activate calcium-binding sites in basophils even when no secretion is observed in the presence of calcium. It is suggested that the degree of secretion observed from basophils depends on the number of occupied Fc receptors for IgE and the coupling of these Fc receptors to calcium transport sites. 相似文献
13.
In order to assess the importance of the chronic increase in precursor availability on central histaminergic mechanisms in rats, nine male Wistar rats received L-histidine orally at a dose of 1000 mg/kg, twice daily (07.00 h and 19.00 h) for 1 week; 9 rats were used as controls. Brain tissue histamine and tele-methylhistamine levels, as well as plasma histamine concentration were assayed. Binding properties and regional distribution of the autoregulatory histamine H3 receptors in brain were studied with [3H]-R-alpha-methylhistamine receptor binding and autoradiography. In L-histidine loaded rats, tissue histamine levels in cortex, hypothalamus, and rest of the brain were significantly increased by 40%-70%. Histamine concentrations in cerebellum and plasma, and tele-methylhistamine concentrations in cortex and hypothalamus did not change. The binding properties of H3 receptors in cortex were not altered. However, there were changes in the regional distribution of [3H]-R-alpha-methylhistamine binding sites, suggestive of a region-selective up-/down-regulation of histamine H3 receptors or their receptor sub-types. These results imply that following repeated L-histidine administration in the rat (1) there is enhanced synthesis of brain histamine not reflected in its functional release; (2) the excess of histamine is sequestered and stored rather than being metabolized; (3) histamine H(3) receptor binding properties are not altered, whereas receptor density is changed in selected regions. In conclusion, these results demonstrate that the neuronal mechanisms controlling histamine synthesis, storage, and release are adaptable and allow the sequestration of the excess of histamine in order to prevent excessively high neuronal activity. 相似文献
14.
Saturable binding of [3H]histamine in equilibrium with homogenates of rat cerebral cortex reveals Hill coefficients between 0.4 and 1.0, depending upon the conditions. Data from individual experiments are well described assuming one or two classes of sites. Only the sites of higher affinity (KP1 = 3.9 +/- 0.5 nM) are observed when binding is measured by isotopic dilution at a low concentration of the radioligand (less than 1.5 nM) in the presence of magnesium or by varying the concentration of the radioligand. The sites of lower affinity (KP2 = 221 +/- 26 nM) appear during isotopic dilution at higher concentrations of the radioligand or at lower concentrations either upon the addition of guanylyl imidodiphosphate (GMP-PNP) or upon the removal of magnesium. Estimates of the second- and first-order rate constants for association and dissociation of [3H]histamine agree well with KP1. Apparent capacities corresponding to KP1 and KP2 are of the order of 100 ([R1]t) and 1300 pmol/g of protein ([R2]t), respectively. Simple interconversion cannot account for the changes in binding that occur upon adding GMP-PNP or removing magnesium, since the increase in [R2]t exceeds the decrease in [R1]t. Moreover, the apparent amount of high-affinity complex exhibits a biphasic dependence on the concentration of [3H]histamine; an increase at low concentrations is offset by a decrease that occurs at higher concentrations. The latter appears to be positively cooperative and concomitant with formation of the low-affinity complex. These and other observations indicate that the binding of histamine is inconsistent with models commonly invoked to rationalize the binding of agonists to neurohumoral receptors. GMP-PNP and magnesium reciprocally alter capacity at the sites of higher affinity, however, and the reduction caused by GMP-PNP reflects a substantial increase in the rate constant for dissociation at the sites that appear to be lost. The sites labeled by [3H]histamine thus reveal the properties of neurohumoral receptors linked to a nucleotide-specific G/F protein. 相似文献
15.
Biexponential Kinetics of (R)-α-[3 H]Methylhistamine Binding to the Rat Brain H3 Histamine Receptor 总被引:3,自引:0,他引:3
Robert E. West Jr. Adam Zweig Russell T. Granzow Marvin I. Siegel Robert W. Egan 《Journal of neurochemistry》1990,55(5):1612-1616
The H3 histamine receptor is a high-affinity receptor reported to mediate inhibition of CNS histidine decarboxylase activity and depolarization-induced histamine release. We have used (R)-alpha-[3H]methylhistamine, a specific, high-affinity agonist, to characterize ligand binding to this receptor. Saturation binding studies with rat brain membranes disclosed a single class of sites (KD = 0.68 nM; Bmax = 78 fmol/mg of protein). Competition binding assays also yielded an apparently single class of sites with a rank order of potency for ligands characteristic of an H3 histamine receptor: N alpha-methylhistamine, (R)-alpha-methylhistamine greater than histamine, thioperamide greater than impromidine greater than burimamide greater than dimaprit. In contrast, kinetic studies disclosed two classes of sites, one with fast, the other with slow on-and-off rates. Density of (R)-alpha-[3H]methylhistamine binding followed the order: caudate, midbrain (thalamus and hippocampus), cortex greater than hypothalamus greater than brainstem greater than cerebellum. These data are consistent with an H3 histamine receptor, distinct from H1 and H2 receptors, that occurs in two conformations with respect to agonist association and dissociation or with multiple H3 receptor subtypes that are at present pharmacologically undifferentiated. 相似文献
16.
Saras A Gisselmann G Vogt-Eisele AK Erlkamp KS Kletke O Pusch H Hatt H 《The Journal of biological chemistry》2008,283(16):10470-10475
Histamine is not only a crucial cytokine in the periphery but also an important neurotransmitter and neuromodulator in the brain. It is known to act on metabotropic H1-H4 receptors, but the existence of directly histamine-gated chloride channels in mammals has been suspected for many years. However, the molecular basis of such mammalian channels remained elusive, whereas in invertebrates, genes for histamine-gated channels have been already identified. In this report, we demonstrated that histamine can directly open vertebrate ion channels and identified beta subunits of GABA(A) receptors as potential candidates for histamine-gated channels. In Xenopus oocytes expressing homomultimeric beta channels, histamine evoked currents with an EC(50) of 212 microm (beta(2)) and 174 microm (beta(3)), whereas GABA is only a very weak partial agonist. We tested several known agonists and antagonists for the histamine-binding site of H1-H4 receptors and described for beta channels a unique pharmacological profile distinct from either of these receptors. In heteromultimeric channels composed of alpha(1)beta(2) or alpha(1)beta(2)gamma(2) subunits, we found that histamine is a modulator of the GABA response rather than an agonist as it potentiates GABA-evoked currents in a gamma(2) subunit-controlled manner. Despite the vast number of synthetic modulators of GABA(A) receptors widely used in medicine, which act on several distinct sites, only a few endogenous modulators have yet been identified. We show here for the first time that histamine modulates heteromultimeric GABA(A) receptors and may thus represent an endogenous ligand for an allosteric site. 相似文献
17.
Adam Zweig Marvin I. Siegel Robert W. Egan Mike A. Clark Robert G. L. Shorr Robert E. West Jr. 《Journal of neurochemistry》1992,59(5):1661-1666
The H3 receptor is a high-affinity histamine receptor that inhibits release of several neurotransmitters, including histamine. We have characterized H3 receptor binding in bovine brain and developed conditions for its solubilization. Particulate [3H]histamine binding showed an apparently single class of sites (KD = 4.6 nM; Bmax = 78 fmol/mg of protein). Of the detergents tested, digitonin at a detergent/protein ratio of 1:1 (wt/wt) yielded the greatest amount of solubilized receptors, typically 15-30% of particulate binding. Neither equilibrium binding of [3H]histamine to receptors (KD = 6.1 nM; Bmax = 92 fmol/mg of protein) nor the inhibitor profile was substantially altered by digitonin solubilization. However, solubilization did increase the rate of [3H]histamine association with and dissociation from the receptor. Size-exclusion chromatography indicated an apparent molecular weight of 220,000 for the solubilized receptor, and peak binding from this column retained its guanine nucleotide sensitivity. These last two observations are consistent with the solubilized receptor occurring in complex with a guanine nucleotide-binding protein. 相似文献
18.
Histamine membrane receptors are defined as either H1 (blocked by diphenhydramine-like antagonists) or H2 (blocked by cimetidine-like agents). We now report the solubilization, separation, and partial characterization of specific H1 and H2 membrane receptors from calf thymocytes. Membrane fragments were incubated with [3H]histamine either alone or with unlabeled histamine, diphenhydramine, or cimetidine. Maximal specific binding occurred with incubation at 37 degrees C for 2 h at a concentration of 5 x 10(-6) M [3H]histamine. Labeled receptors were solubilized from membranes with 0.3 M KCl and 1% Nonidet 40. Chromatography of the solubilized labeled receptors on ion exchange columns revealed two classes of receptor. One class bound to DEAE-cellulose and eluted as a sharp peak at 0.15 M NaCl/Pi. The other bound to phosphocellulose and eluted as a sharp peak at 0.55 M NaCl/Pi. Initial incubation of the membranes in the presence of the H1 receptor antagonist diphenhydramine virtually abolished the DEAE-cellulose peak, while incubation with cimetidine, the H2 receptor antagonist, blocked the phosphocellulose peak. We conclude that H1 and H2 histamine receptors are physically separable and can be defined by their ability to bind to either DEAE-cellulose or phosphocellulose. 相似文献
19.
Histamine is known to act, at least in part, as a growth factor for several cell types, and as production of this biogen amine has been found to accelerate the rate of tissue proliferation in wound repair, embryogenesis and malignant growth. Abundant experimental and clinical data suggest that histamine augments in vivo tumour cell proliferation via histamine H2 receptors (H2R). Here, we report that exogenously added histamine stimulates Ets-1 (v-ets erythroblastosis virus E26 oncogene homolog 1) synthesis in human melanoma cells. Involvement of histamine receptors in the histamine induced ets-1 expression has been also studied. Our data show that these newly recognized actions of histamine are mediated by the H2R. Modification of local protooncogen Ets-1 level is likely being involved in the regulation of melanoma growth. 相似文献
20.
M Imoto K Tsuchie M Tanaka S Sugiyama T Ozawa 《Biochemical and biophysical research communications》1985,127(3):885-889
We quantitatively determined the receptors for histamine H1, histamine H2, alpha- and beta-adrenergic, prostaglandin E2 and F2 alpha in liver plasma membranes. The number of the receptors was the greatest in histamine H1 receptors (4740 +/- 750 fmol/mg protein) and the second in alpha-adrenergic receptors (965 +/- 16). Although relatively small numbers of the receptors were observed for histamine H2 (116 +/- 11) and prostaglandin E2 (38.0 +/- 8.9), we could not determine the number and affinity of beta-adrenergic and prostaglandin F2 alpha receptors. In contrast to the number of receptors, there was not significant difference in the affinities of receptors for histamine H1, histamine H2, alpha-adrenergic hormone and prostaglandin E2. These results suggest that histamine and its receptor play some role in liver function. 相似文献