1,721,190 research outputs found
Dual regulation of ACTH secretion by guanine nucleotides in permeabilized AtT-20 cells
No full text1. We have examined the effects of guanine nucleotides on ACTH secretion from digitonin-permeabilized AtT-20 cells, with the aim of analyzing the involvement of GTP-binding proteins (G proteins) in the secretory process. 2. AtT-20 cells permeabilized with 20 microM digitonin displayed calcium-dependent secretion. The EC50 of calcium was approximately 2 microM and the maximal stimulation was 350% of basal release. 3. Nonhydrolyzable guanine nucleotides also stimulated ACTH release, in a virtually Ca2+-free medium. The EC50 of guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) was approximately 15 microM and the maximal stimulation was approximately 230% of basal release. The effects of calcium and guanine nucleotides were not additive. 4. In the presence of the inhibitory hormone, somatostatin guanine nucleotides inhibited the calcium-stimulated secretion. 5. Both the stimulatory and the inhibitory effects on secretion of guanine nucleotides were independent of changes in cyclic AMP (cAMP) and calcium. It is suggested that G proteins influence an unknown step in the secretion process, which would be near or at the exocytotic site. 6. The results can be explained by assuming the existence of two types of G proteins, one with stimulatory effects on exocytotic release (GeS) and another with inhibitory effects (GeI)
The physiology of membrane transport and endomembrane-based signalling
No full textSome of the important open questions concerning the physiology of the secretory pathway relate to its homeostasis. Secretion involves a number of separate compartments for which their transport activities should be precisely cross-coordinated to avoid gross imbalances in the trafficking system. Moreover, the membrane fluxes across these compartments should be able to adapt to environmental 'requests' and to respond to extracellular signals. How is this regulation effected? Here, we consider evidence that endomembrane-based signalling cascades that are similar in organization to those used at the plasma membrane coordinate membrane traffic. If this is the case, this would also represent a model for a more general inter-organelle signalling network for functionally interconnecting different intracellular activities, a necessity for the maintenance of cellular homeostasis and to express harmonic global cellular responses
Response from Facchiano, Innamorati and Luini
No full textCoffield et al. discuss three hypotheses that have been proposed recently for the mode of action of the clostridial neurotoxins. They conclude that the mechanism of toxin action suggested by Schiavo et al. ‘v2, that is, by proteolytic cleavage of essential synaptic proteins, is supported by substantial evidence and explains toxin-induced neuroparalysis elegantly. By contrast, they suggest that there are reasons to be cautious about the other two hypotheses, which implicate the enzymes transglutaminase (TGase)“,4 and phospholipase A, (PLA,)’ in the neuroparalytic effects of the toxins. We could not agree more about the power and elegance of the proteolytic mechanism first demonstrated by Cesare Montecucco and colleagues, and later confirmed by Link et aL6. Indeed, we believe that their idea that the short-term effects of clostridial toxins depend on the proteolysis of proteins essential for exocytosis’ is sound, and will be rapidly and universally accepted
Evidence that receptor-linked G protein inhibits exocytosis by a post-second-messenger mechanism in AtT-20 cells
No full textIn AtT-20 cells somatostatin inhibits the secretion of adrenocorticotropic hormone (ACTH) through the activation of GTP binding proteins (G proteins) linked to second messengers such as calcium and cyclic AMP (cAMP). Recently, it has been proposed that there may be G proteins that regulate directly the exocytotic machinery. We have investigated whether somatostatin could inhibit secretion at a step distal to second messengers through a GTP binding protein. For these studies two experimental paradigms were used: (1) intact cells stimulated by calcium ionophores and (2) digitonin-permeabilized cells exposed to buffers of increasing Ca2+ concentrations. Somatostatin inhibited by 70% the ACTH release caused by the calcium ionophore ionomycin without modifying the ionophore-induced elevation in cytosolic [Ca2+]. This effect was cAMP independent because (1) it was observed in the presence of high concentrations of membrane-permeant cAMP analogues, and (2) it was not accompanied by a change in cAMP levels. The effect was also independent of the levels of activators of protein kinase C because it could be produced in the presence of high concentrations of phorbol esters. The action of somatostatin was prevented by pertussis toxin. In digitonin-permeabilized AtT-20 cells somatostatin inhibited release induced by calcium buffers in a GTP-dependent manner. These two observations indicate the involvement of a G protein. It is proposed that a G protein coupled to somatostatin receptors inhibits the intracellular machinery of secretion at a step distal to second messengers, perhaps at the exocytotic site
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Norepinephrine and thyrotropin stimulation of iodide efflux in FRTL-5 thyroid cells involves metabolites of arachidonic acid and is associated with the iodination of thyroglobulin
No full textThe transglutaminase hypothesis for the action of tetanus toxin
No full textTetanus toxin potently and almost irreversibly inhibits the release of neurotransmitters from nerve terminals. The toxin binds to and activates transglutaminase, a Ca2+-dependent enzyme that can form stable crosslinks between substrate proteins. Transglutaminase is present in nerve terminals and recognizes synapsin I, an abundant synaptic vesicle phosphoprotein involved in neurotransmission, as an excellent substrate. The neuroparalytic action of tetanus toxin might be due, at least in part, to the stimulation of synaptic transglutaminase and the consequent crosslinking of synapsin I. © 1993
Association of the changes in cytosolic Ca2+ and iodide efflux induced by thyrotropin and by the stimulation of alpha 1-adrenergic receptors in cultured rat thyroid cells
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