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1.
Leslie A. Holladay Phillip Wilder 《Biochimica et Biophysica Acta (BBA)/General Subjects》1980,629(1):156-167
The effect of cationic, anionic and nonionic detergents on the EPR spectrum of spin-labeled somatostatin has been studied. At detergent concentrations well above the critical micelle concentration, nonionic detergents do not alter the EPR spectrum. Sodium dodecyl sulfate markedly alters both the line height ratio and the hyperfine splitting constant, whilst dodecyltrimethylammonium bromide alters only slightly the hyperfine splitting constant and line height ratio. The somatostatin-sodium dodecyl sulfate complex appeared monodisperse by sedimentation equilibrium with about 17 g bound detergent per g peptide. Circular dichroic and difference spectra of the dodecyl sulfate-somatostatin complex show that the tryptophanyl residue is buried in a nonpolar environment and that the secondary and tertiary structure of the peptide is markedly altered. Sedimentation equilibrium studies suggest that two types of dodecyltrimethylammonium-somatostatin complex exist. One type resembles the dodecyl sulfate-peptide complex, whilst the other appears to include several peptide units with only about one gram bound detergent per gram peptide. 相似文献
2.
Summary Two monoclonal antibodies directed against somatostatin 14 were used to study immunoreactive neurons, their processes and their synapses in the cat retina. In retinal whole-mounts, a sparse population of wide-field displaced amacrine cells was observed predominantly in the ventral retina and near the retinal margin. Processes of these cells ramified mainly in two distinct strata within the inner plexiform layer: one near the inner nuclear layer (INL), and the other near the ganglion cell layer (GCL). The length of immunoreactive fibres within each plexus was measured: 232±32 mm/mm2 near the INL and 230±74 mm/mm2 near the GCL in all retinal regions. The immunoreactive processes were studied using electron-microscopic techniques; conventional and some ribbon-containing synapses (dyads) were found. Immunolabelled processes received input synapses from other amacrine cell processes. These investigations provide further evidence that this cell population has a diffuse, regulatory or modulatory role for visual-information processing in the inner plexiform layer. 相似文献
3.
H Christ 《Peptides》1985,6(1):139-148
Administration of 10 and 30 micrograms methionine-enkephalin (MET-ENK)/g bw (n = 10/dose) affected the propensity towards fighting in H. bimaculatus; 10 micrograms increased, while 30 micrograms decreased the aggressive behavior. MET-ENK also affected a number of behavior patterns displayed by the fish. Moreover, the "wet-dog-shakes" observed suggest that MET-ENK acts on opiate-receptors. Treatment with substance P (SP)/g bw (n = 10/dose) induced chafing movements in the fish slightly. It also decreased fighting and increased biting of the air stone, which is evidence that H. bimaculatus is still aggressive, directing its attacks to different objects. When 4, 8, 12 micrograms somatostatin (SRIF)/g bw (n = 10/dose) were injected, H. bimaculatus stopped fighting for several hours after the onset of treatment, depending on the dosage. Somatostatin reduces blood glucose concentration, causing a sudden stop of aggressive behavior, 0.04, 0.1, 0.6, 1.0 and 3.0 IU prolactin (PRL)/g bw (n = 5/dose) eventually decreased fighting and affected a number of behavior patterns displayed by the fish. 相似文献
4.
The effects of iontophoretically applied human pancreatic growth hormone-releasing factor (hpGRF), peptide histidine isoleucine (PHI-27), and somatostatin (SS) on the extracellular activity of single cells in the hypothalamus, thalamus, and cortex of the rat brain were studied in urethane-anesthetized, male rats. Neurons with membrane sensitivity to hpGRF, PHI-27, and SS were present in each brain region. Although neurons excited by these peptides were encountered in thalamus and hypothalamus, depression of neuronal firing was the predominant response observed. Overall, the neurons responding to hpGRF also possessed membrane sensitivity to PHI-27, whereas, the hpGRF sensitive neurons appeared to be more divided as to their ability to respond to SS. The results clearly demonstrate that hpGRF and PHI-27 are capable of affecting the membrane excitability of neurons in several brain regions. The distribution of neurons sensitive to hpGRF suggests that hypothalamic GRF, in addition to its well documented role in the regulation of pituitary growth hormone secretion, may subserve other physiological events in the rat central nervous system as a neurotransmitter and/or neuromodulator. 相似文献
5.
Actions of Excitatory Amino Acids on Somatostatin Release from Cortical Neurons in Primary Cultures 总被引:1,自引:1,他引:0
L-Glutamate, N-methyl-D-aspartic acid (NMDA), quisqualate, and kainate were found to increase endogenous somatostatin release from primary cultures of rat cortical neurons in a dose-dependent manner. The rank order of potency calculated from the dose-response curves was quisqualate greater than glutamate = NMDA greater than kainate, with EC50 values of 0.4, 20, and 40 microM, respectively. Alanine, glutamine, and glycine did not modify the release of somatostatin. The stimulation of somatostatin release elicited by L-glutamate was Ca2+ dependent, was decreased by Mg2+, and was blocked by DL-amino-5-phosphonovaleric acid (APV) and thienylphencyclidine (TCP), two specific antagonists of NMDA receptors. The NMDA stimulatory effect was strongly inhibited by APV in a competitive manner (IC50 = 50 microM) and by TCP in a noncompetitive manner (IC50 = 90 nM). The release of somatostatin induced by the excitatory amino acid agonists was not blocked by tetrodotoxin (1 microM), a result suggesting that tetrodotoxin-sensitive, sodium-dependent action potentials are not involved in the effect. Somatostatin release in response to NMDA was potentiated by glycine, but the inhibitory strychnine-sensitive glycine receptor did not appear to be involved. Our data suggest that glutamate exerts its stimulatory action on somatostatin release essentially through an NMDA receptor subtype. 相似文献
6.
A method has been developed for the study of somatostatin (SS) binding to dissociated cells from rat cerebral cortex. Binding of [125I][Tyr11]SS to cells obtained by mechanical dissociation of rat cerebral cortex was dependent on time and temperature, saturable, reversible and highly specific. Under conditions of equilibrium, i.e., 60 min at 25°C, native SS inhibited tracer binding in a dose-dependent manner. The Scatchard analysis of binding data was linear and yielded a dissociation constant of 0.60±0.08 nM with a maximal binding capacity of 160±16 fmol/mg protein. The binding of [125I][Tyr11]SS was specific as shown in experiments on tracer displacement by the native peptide, SS analogues, and unrelated peptides. 相似文献
7.
Abstract: Thioperamide (2 mg/kg, i.p.), a histamine H3 -receptor antagonist, increased the number of somatostatin (SS) receptors, with no change in the affinity constant, in the rat frontoparietal cortex. This effect was prevented by treatment with ( R )-α-methylhistamine (3.2 mg/kg, i.p.), a histamine H3 -receptor agonist. Thioperamide also induced an increase in SS binding in rats pretreated with mepyramine, a histamine H1 -receptor antagonist, or cimetidine, a histamine H2 -receptor antagonist. Pretreatment with mepyramine plus cimetidine administered simultaneously antagonized the thioperamide effect on SS binding. The increase in the number of SS receptors was accompanied by a greater SS-mediated inhibition of basal and forskolin-stimulated adenylyl cyclase (AC) activity in frontoparietal cortical membranes in the thioperamide group. Furthermore, the functional activity of the guanine nucleotide-binding inhibitory protein (Gi protein) was not altered by thioperamide or ( R )-α-methylhistamine administration in frontoparietal cortical membranes. In rats treated with mepyramine plus thioperamide or cimetidine plus thioperamide, the increase in the number of SS receptors was also accompanied by an increased SS inhibition of AC activity. Thioperamide induced a significant increase in SS-like immunoreactivity content in the frontoparietal cortex. Altogether, these results suggest that frontoparietal cortical histamine may play, at least in part, a role in the regulation of the somatostatinergic system. 相似文献
8.
An examination of the binding characteristics of a large number of somatostatin analogues with respect to the five known somatostatin receptor subtypes has recently resulted in the discovery of several peptides with some selectivity for types 2, 3, and 4 and little affinity for type 1 or 5 receptor. A panel of these peptides has thus far implicated type 2 receptors in the inhibition of release of pituitary growth hormone and type 4 receptors in inhibiting pancreatic insulin release. In the present article, we have examined the inhibitory effects of the same group of peptides on in vivo rat gastric acid and pancreatic amylase release and binding to rat pancreatic acinar cells. The type 2-selective ligand NC-8–12 was a potent inhibitor of gastric acid release (EC50s in the 1.5 nM region) whereas the type 4-selective ligand, DC-23–99, elicited little response. However, some involvement of type 3 receptors could not be ruled out because the type 3-selective analoueg, DC-25–20, exhibited inhibitory effects at higher dose levels (EC50 > 10 nM). Conversely, the type 4 analogue was a potent inhibitor of amylase release (EC50 1.1 nM) whereas the type 3 analogue had no significant effects at doses tested. DC-23–99 also bound with high affinity to rat acinar cells (EC50 3.8 nM), whereas DC-25-20 exhibited more than 10-fold less affinity. Thus, these two major biological functions of somatostatin appear to be controlled by different receptors and, furthermore, effects on both endocrine and exocrine pancreas appear to be type 4 receptor mediated. 相似文献
9.
Since the positive charge on the lysine residues plays an important role in the receptor recognition ability of oLH, the hormonotoxin has been synthesised with the use of 2-iminothiolane HC1 (2IT) and N-Succinimidyl-3-(2-pyridyldithio)-propionate (SPDP). The oLH activated with 2IT (oLH-10) was then mixed with SPDP activated gelonin (gelonin-30) in order to obtain a oLH-S-S-gelonin hormonotoxin. The conjugation mixture containing hormonotoxin was purified by gel-filtration chromatography according to the molecular weight and a complete physico-chemical, immunochemical and biochemical analysis were performed. The linkage occured through the -NH2 groups of -subunit of oLH as judged from RP-HPLC analysis. A 11 (oLH:gelonin) molar ratio was obtained when determined with the use of several techniques. The hormonotoxins retained substantial receptor binding, steroidogenic activity and immunoreactivity. The competitive displacement analysis indicate that the binding occurs via the hormone part leaving the gelonin free which was probed with the gelonin antibodies. The presently described (C150A-02, C160A-02 and C170A-02) hormonotoxins exhibited higher receptor binding and toxicity to the target cells than the hormonotoxins prepared with the use of SPDP only. Therefore it is concluded that higher receptor binding and cytotoxicity may be due to the retention of positive charge on the lysine residues of oLH which was preserved during the conjugation process.Abbreviations BSA
Bovine Serum Albumin
- CMC
Carboxy methyl Cellulose
- DTT
Dithiothreitol
- DMEM
Dulbeco's Modified Eagle's Medium
- DTNB
Ellman's reagent [5,5-dithio-bis-(2-nitrobenzoic acid)]
- EDTA
Ethylenediaminetetraacetic acid
- FPLC
Fast Protein Liquid Chromatography
- FCA
Freund's Complete Adjuvant
- FCS
Fetal Calf Serum
- Gelonin-30
Gelonin modified by SPDP
- GnRH
Gonadotropin-Releasing Hormone
- Gelonin-SPDP
SPDP modified derivative of gelonin
- HEPES
(N-[2-hydroxyethyl] piperazine-N-[-2-ethanesulphonic acid])
- IFA
Incomplete Freund's Adjuvant
- 2IT
2-Iminothiolane
- IODOGEN
1,3,4,6-tetrachloro 3,6-diphenylglycouril
- oLH
Ovine Luteinizing Hormone
- oLH-SPDP
SPDP modified derivative of oLH
- oLH-10
oLH modified by 2IT
- oLH2IT
Molar ratio of oLH and 2IT
- PDP
2-Pyridyl-dithiopropionate
- PAP
Pokeweed Antiviral Protein
- RIP
Ribosome Inactivating Protein
- RP-HPLC
Reverse-Phase High Performance Liquid Chromatography
- RPMI
Roswell Park Memorial Institute
- RIA
Radioimmunoassay
- RRA
Radioreceptor Assay
- SPDP
N-Succinimidyl-3(2-pyridyldithio)propionate
- SDS-PAGE
Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis
- TCA
Trichloroacetic acid
- TFA
Trifluroacetic acid 相似文献
10.