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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Aridor, M. Traub, L. M. Sagi-eisenberg, R. |
| Description | Author Affiliation: Aridor M ( Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.) |
| Abstract | Histamine release induced by the introduction of a nonhydrolyzable analogue of GTP, GTP-gamma-S, into ATP-permeabilized mast cells, is associated with phosphoinositide breakdown, as evidenced by the production of phosphatidic acid (PA) in a neomycin-sensitive process. The dependency of both PA formation and histamine secretion on GTP- gamma-S concentrations is bell shaped. Whereas concentrations of up to 0.1 mM GTP-gamma-S stimulate both processes, at higher concentrations the cells' responsiveness is inhibited. At a concentration of 1 mM, GTP- gamma-S self-inhibits both PA formation and histamine secretion. Inhibition of secretion can, however, be overcome by the basic secretagogues compound 48/80 and mastoparan that in suboptimal doses synergize with 1 mM GTP-gamma-S to potentiate secretion. Secretion under these conditions is not accompanied by PA formation and is resistant both to depletion of Ca2+ from internal stores and to pertussis toxin (PtX) treatment. In addition, 48/80, like mastoparan, is capable of directly stimulating the GTPase activity of G-proteins in a cell-free system. Together, our results are consistent with a model in which the continuous activation of a phosphoinositide-hydrolyzing phospholipase C (PLC) by a stimulatory G-protein suffices to trigger histamine secretion. Basic secretagogues of mast cells, such as compound 48/80 and mastoparan, are capable of inducing secretion in a mechanism that bypasses PLC by directly activating a G-protein that is presumably located downstream from PLC (GE). Thereby, these secretagogues induce histamine secretion in a receptor-independent manner. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 3 |
| Volume Number | 111 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 1990-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Exocytosis Physiology GTP-Binding Proteins Mast Cells Metabolism Adenosine Triphosphate Animals Brain Enzymology Cell Membrane Permeability Drug Effects GTP Phosphohydrolases Guanosine 5'-O-(3-Thiotriphosphate) Guanosine Triphosphate Analogs & Derivatives Pharmacology Histamine Release Membranes Peptides Pertussis Toxin Phosphatidic Acids Rats, Inbred Strains Thionucleotides Type C Phospholipases Virulence Factors, Bordetella Wasp Venoms P-Methoxy-N-methylphenethylamine Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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