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Opioids and central baroreflex control: a site of action in the nucleus tractus solitarius 总被引:1,自引:0,他引:1
F J Gordon 《Peptides》1990,11(2):305-309
These studies investigated whether the nucleus of the tractus solitarius (NTS) is a central site where opioids modulate baroreceptor reflexes. Microinjections into the NTS of [D-Ala2,MePhe4, Gly-ol5]enkephalin (DAGO) significantly reduced reflex-mediated depressor responses evoked by electrical stimulation of the aortic nerve. Subsequent NTS injections of naloxone restored baroreflexes to control levels. These results demonstrate that the NTS is a central site where exogenously administered opioids can modulate baroreceptor reflexes. NTS injections of naloxone had no effect on baroreflex function, suggesting that tonic activation of opioid receptors at this site plays little or no role in central baroreflex control. 相似文献
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Gordon Tollin 《Journal of bioenergetics and biomembranes》1995,27(3):303-309
Photoexcitation of flavin analogs generates the lowest triplet state (via intersystem crossing from the first excited singlet state) in the nanosecond time domain and with high quantum efficiency. The triplet, being a strong oxidant, can abstract a hydrogen atom (or an electron) from a reduced donor in a diffusion-controlled reaction. If the donor is a redox protein, the oxidation process can be used to initiate an electron transfer sequence involving either intramolecular or intermolecular reactions. If the donor is an organic compound such as EDTA, the neutral flavin semiquinone will be produced by H atom abstraction; this is a strong reductant and can subsequently transfer a hydrogen atom (or an electron) to an oxidized redox protein, thereby again initiating a sequence of intramolecular or intermolecular processes. If flavin photoexcitation is accomplished using a pulsed laser light source, the initiation of these protein electron transfer reactions can be made to occur in the nanosecond to microsecond time domain, and the sequence of events can be followed by time-resolved spectrophotometry to obtain rate constants and thus mechanistic information. The present paper describes this technology, and selected examples of its use in the investigation of redox protein mechanisms are given. 相似文献
25.
Hydrogen peroxide is more toxic to mammalian cells at 37 degrees C than 0 degree C at all concentrations studied. Histone-free nuclei (nucleoids) extracted from treated cells have a reduced ability to maintain positive DNA supercoiling, with the maximum effect at the higher temperature. Prior exposure of cells to sodium ascorbate at 0 degree C increased both toxicity and the inhibition of nuclear supercoil rewinding. After exposure at 0 degrees C, normal levels of supercoiling returned with both a fast and a slow component, kinetics characteristic of DNA single-strand break repair; the fast component was eliminated when cells were exposed at 37 degrees C due to in situ rejoining. At least a portion of the lethal lesions induced by hydrogen peroxide are DNA double-strand breaks (dsb) because the dsb repair-deficient mutant, xrs-5, is approximately two to three times more sensitive than wild-type cells over the initial portion of the survival curve. However, the increased toxicity found after exposure at 37 degrees C is observed equally in both cell lines, indicating that temperature-dependent cell killing is not directly linked to DNA dsb. It is suggested that cell killing at 37 degrees C is mediated through two linked processes. First, hydrogen peroxide may disrupt cation-stabilized nuclear supercoiling by direct ion oxidation. Second, as a part of the oxidation process, hydrogen peroxide will produce potentially cytotoxic free radicals close to the DNA-linked metal site, limited in extent only by the presence of chemicals capable of reducing metal ions prior to reoxidation. 相似文献
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Human bone marrow contains a population of haemopoietic progenitor cells that can be distinguished by their ability to adhere to preformed stromal layers (cultured in the presence of methylprednisolone [MP+] and form blast cell colonies. The stromal layers function in the colony assay after they have been heavily irradiated but not after they have been passaged. The binding of the progenitor cells to the stromal cells is complete after 2 hours of coincubation, and stromal layers of 9.6 cm2 can provide adhesion sites for at least 2,000 blast colony-forming cells. The blast colony-forming cells were shown by micromanipulation to self-renew as well as to give rise to multipotential and lineage-committed colony-forming progenitor cells. 相似文献
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Two computer models for the binding of estradiol to estrogen receptors were constructed, based solely upon the thermodynamic constraints of the most likely equilibria involved and known equilibrium constants. Previous data had suggested that the positive cooperativity of the system was dependent upon a monomer-dimer equilibrium (Notides et al., Proc. natn. Acad. Sci., U.S.A. 78 (1981) 4926-4930). Using computer modeling, we confirmed that the thermodynamic constraints of a monomer-dimer equilibrium system result in convex Scatchard plots in agreement with experimental data, including the progression to linearity at low receptor concentrations. This technique yielded estimates of the equilibrium constant for dimerization (approx. 10(10) to 10(14) M-1). The dose-response characteristics of the monomer-dimer equilibrium system revealed steep dose-response curves that were sensitive to the receptor concentration. In contrast, the dose-response curves that did not undergo a monomer-dimer equilibrium system and had a single step equilibrium process were more gradual. 相似文献
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N Rakieten B S Gordon A Beaty R W Bates P S Schein F G Standaert 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1976,151(3):632-635
Hypoglycemic rats bearing insulin-secreting islet-cell adenomas produced by the combined action of streptozotocin and nicotinamide were treated with streptozotocin. Antitumor response was demonstrated by elevation of blood glucose, reduction in plasma and tumor IRI, and histopathologic changes in the beta-cell neoplasm. The rodent tumor model may serve as a predictive system for selection and investigation of mechanisms of action of future antitumor agents to be used in the treatment of malignant insulinoma in man. 相似文献