ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.3169466

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

G proteins are a highly conserved family of membrane‐associated proteins composed of α, β, and γ subunits. The α subunit, which is unique for each G protein, binds GDP or GTP. Receptors such as those for β‐ and α‐adrenergic catecholamines, muscarinic agonists, and the retinal photoreceptor rhodopsin, catalyze the exchange of GDP for GTP binding to the α subunit of a specific G protein. Gα · GTP regulates appropriate effector enzymes such as adenylyl cyclase or the cyclic GMP phosphodiesterase. The βγ‐subunit complex of G proteins is required for efficient receptor‐catalyzed a subunit guanine nucleotide exchange and also functions as an attenuator of α subunit activation of effector enzymes. Recent elucidation of both receptor and G protein primary sequence has allowed structural predictions and new experimental approaches to study the mechanism of receptor‐catalyzed G protein regulation of specific effector systems and the control of cell function including metabolism, secretion, and growth.—Weiss, E. R.; Kelleher, D. J.; Woon, C. W.; Soparkar, S.; Osawa, S.; Heasley, L. E.; Johnson, G. L. Receptor activation of G proteins.FASEB J.2: 2841‐2848; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.3139484

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

The study of the motor cortex in behaving monkeys during the past 20 years has provided important information on the brain mechanisms underlying motor control. With respect to reaching movement in space, a key role of motor cortex in specifying the direction of reaching has been proposed on the basis of results from studies of the activity of cells and cell populations during reaching. These results and ideas are reviewed and discussed in the context of recent findings concerning the spinal mechanisms underlying reaching movements.— Georgopoulos, A. P. Neural integration of movement: role of motor cortex in reaching.FASEB J.2: 2849‐2857; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.3139485

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Because of the proximity of many bound receptors or enzymes, a membrane surface may become uniformly reactive so that every collision between a ligand and the membrane particle results in a binding or catalytic event. At this limit (the collisional limit), the reaction rate depends on membrane particle (cell) concentration and is independent of receptor concentration. Many receptor systems display properties that satisfy the requirements of a collisionally limited reaction. These include the presence of many receptors per cell. The filling of only a few of these receptors often generates the maximum cellular response, and the remaining receptors have been referred to as spare receptors. However, many receptors are needed to produce the collisional limit, and spare receptors may represent nature's evolution toward a reaction that provides the maximum rate as well as the maximum sensitivity to a ligand. Since receptors or enzymes provided on small membrane fragments will not function at the collisional limit, properties of reconstituted enzymes or receptors may not be extrapolated to the physiological situation. The use of normal bimolecular kinetic or equilibrium equations is inappropriate for reactions limited by collision and can give unusual results that lead to inappropriate conclusions. Determination of whether the collisional limit applies to a membrane‐bound system is important for understanding its properties and those of the physiological circumstance.— Abbott, A. J.; Nelsestuen, G. L. The collisional limit: an important consideration for membrane‐associated enzymes and receptors.FASEB J.2: 2858‐2866; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.2844615

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Species such as superoxide radical (O2−), hydrogen peroxide (H2O2), hydroxyl radical (·OH), and hypochlorous acid (HOC1) can be formed in vivo, e.g., by activated phagocytic cells. Generation of·OH from H2O2in vivo usually involves iron‐dependent reactions. Good evidence exists for increased generation of oxidants in vivo in patients with active rheumatoid disease, but the contribution of these oxidants to the disease process is still uncertain. The likelihood that anti‐inflammatory drugs used in the treatment of arthritis could act by scavenging oxidants or preventing their formation is discussed.— Halliwell, B.; Hoult, J. R.; Blake, D. R. Oxidants, inflammation, and anti‐inflammatory drugs.FASEB J.2: 2867‐2873; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.2844616

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Daily rhythms of secretion have been described for luteinizing hormone (LH) and prolactin (PRL) from the anterior pituitary of rats. Using selective opioid antagonists, we found that μ andxopioid receptor ligands regulate LH and PRL secretion and, of particular interest, that the magnitude of opioidergic effects varies with the time of day. In addition, incomplete temporal overlapping of the LH and PRL responses to the antagonists suggests that different endogenous opioid pathways, with different temporal profiles of peptide release, may control each of these hormones.— Almeida, O. F. X.; Nikolarakis, K. E.; Webley, G. E.; Herz, A. Opioid components of the clockwork that governs luteinizing hormone and prolactin release in male rats.FASEB J.2: 2874‐2877; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.2844617

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Plasmodium falciparumandTrypanosoma cruziwere killed by two novel lytic peptides (SB‐37 and Shiva‐1) in vitro. Human erythrocytes infected withP. falciparum, and Vero cells infected withT. cruzi, were exposed to these peptides. The result, in both cases, was a significant decrease in the level of parasite infection. Furthermore, the peptides had a marked cytocidal effect on trypomastigote stages ofT cruziin media, whereas host eukaryotic cells were unaffected by the treatments. In view of the worldwide prevalence of these protozoan diseases and the lack of completely suitable treatments, lytic peptides may provide new and unique chemother‐apeutic agents for the treatment of these infections.—Jaynes, J. M.; Burton, C. A.; Barr, S. B.; Jeffers, G. W.; Julian, G. R.; White, K. L.; Enright, F. M.; Klei, T. R.; Laine, R. A. In vitro cytocidal effect of novel lytic peptides onPlasmodium falciparumandTrypanosoma cruzi. FASEB J.2: 2878‐2883; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.3049204

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Interleukin 1 (IL 1) production is stimulated by infection, cellular injury, and inflammation. This cytokine directs a wide spectrum of host responses. Human interleukin 1α (IL 1α) was used to examine the time course of effects on zinc metabolism as part of the acute phase response. IL 1 produced a transient depression in the serum zinc concentration and increased serum ceruloplasmin. Metallothionein levels were increased in liver 14‐fold after IL 1. Increased expression of metallothionein‐1 and ‐2 genes following IL 1 were observed in liver, bone marrow, and thymus. Pulse‐labeling experiments with i.v.‐administered65Zn showed that IL 1 drastically altered zinc distribution kinetics among tissues. More65Zn was taken up (and/or retained) by the liver, bone marrow, and thymus 6 h after IL 1, whereas correspondingly less65Zn was found in bone, skin, and intestine. Uptake by other tissues was not affected by IL 1. Chromatography of cytosol from tissues with increased65Zn uptake suggests the IL 1‐induced redistribution may be driven by enhanced metallothionein synthesis. Collectively, the results show that IL 1 regulates zinc metabolism and may direct its preferential, tissue‐specific distribution via elevated metallothionein‐1 and ‐2 gene expression.—Cousins, R. J.; Leinart, A. S. Tissue‐specific regulation of zinc metabolism and metallothionein genes by interleukin 1.FASEB J.2: 2884‐2890; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.2458983

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

β‐Adrenergic receptor (βAR) blocking agents with intrinsic sympathomimetic activity (ISA) can induce modest increases in βAR‐stimulated activity, such as rate and force of contraction in cardiac tissue. The molecular basis for this activity has been elusive. Previous studies have suggested that these compounds do not stimulate cyclic AMP (cAMP) formation even though activation of adenylate cyclase is the generally accepted mechanism for βAR promotion of target cell response. In the current studies, we show that several βAR antagonists with ISA (dichloroisoproterenol, pindolol, and celiprolol) stimulate cAMP accumulation five‐, two‐, and threefold, respectively, in S49 lymphoma cells, but only if cells are simultaneously incubated with the diter‐pene forskolin. TheKIvalues observed for inhibition of isoproterenol‐stimulated cAMP accumulation or of βAR ([125I]iodocyanopindolol) binding for each of the β blockers with ISA were comparable in magnitude to their respective EC50values for forskolin‐potentiated cAMP accumulation. The forskolin‐potentiated responses of these compounds were abolished by the βAR‐antagonist propranolol. These results indicate that the ISA of β‐blocking drugs most likely results from a modest βAR‐mediated stimulation of adenylate cyclase activity. The results further suggest that treatment of target cells with forskolin provides a means to define partial agonism at receptors that are linked to stimulation of adenylate cyclase.—Jasper, J. R.; Michel, M. C.; Insel, M. C. Molecular mechanism of β‐adrenergic receptor blockers with intrinsic sympathomimetic activity.FASEB J.2: 2891‐2894; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.2901994

出版商:Wiley    

年代:1988

数据来源: WILEY

摘要:

Effects of deltamethrin, a pyrethroid insecticide, and lindane, the gamma isomer of hexachlorocyclohexane, on the γ‐aminobutyric acid (GABA)‐activated ion channels were studied using cultured neurons isolated from the newborn rat dorsal root ganglia. The neuron was voltage clamped using the whole cell patch clamp technique. Two components of inward chloride currents were generated in response to bath application of GABA. One of the components was selectively blocked by 1 × 10−5M lindane in a stereospecific manner, but neither component was affected by 1 × 10−5M deltamethrin, which drastically prolonged the voltage‐activated sodium channel current. Thus, the action of lindane to stimulate the nervous system is partly because of an interaction with the GABA receptor‐channel complex. The target site of deltamethrin is not the GABA receptor‐channel complex but the sodium channel. The results suggest a multiplicity of the GABAareceptor‐chloride channel complex.— Ogata, N.; Vogel, S. M.; Narahashi, T. Lindane but not deltamethrin blocks a component of GABA‐activated chloride channels.FASEB J.2: 2895‐2900; 1988.

ISSN:0892-6638    

DOI:10.1096/fasebj.2.13.2458984

出版商:Wiley    

年代:1988

数据来源: WILEY