Intracellular mechanism of Pb(2+)-induced norepinephrine release from bovine chromaffin cells
Autor: | Janusz B. Suszkiw, J. L. Tomsig |
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Rok vydání: | 1993 |
Předmět: |
Cell Membrane Permeability
Calmodulin Physiology 8-Bromo Cyclic Adenosine Monophosphate Norepinephrine chemistry.chemical_compound Adenosine Triphosphate Alkaloids medicine Animals Staurosporine Secretion Egtazic Acid Cytochalasin B Cells Cultured Protein Kinase C Protein kinase C Dose-Response Relationship Drug L-Lactate Dehydrogenase biology Activator (genetics) Spectrophotometry Atomic Imidazoles Cell Biology Cyclic AMP-Dependent Protein Kinases Enzyme Activation Kinetics medicine.anatomical_structure Lead chemistry Biochemistry Adrenal Medulla Chromaffin cell biology.protein Biophysics Tetradecanoylphorbol Acetate Calcium Cattle Intracellular medicine.drug |
Zdroj: | American Journal of Physiology-Cell Physiology. 265:C1630-C1636 |
ISSN: | 1522-1563 0363-6143 |
Popis: | The intracellular mechanism of Pb(2+)-induced release of norepinephrine (NE) was investigated in comparison with Ca2+ in bovine chromaffin cells permeabilized with staphylococcal alpha-toxin. Pb2+ activated NE release at considerably lower concentrations [concentration of free metal giving half maximal metal-dependent release (K0.5) 4.6 nM] than Ca2+ (K0.5 2.4 microM). The release of NE was associated with the release of dopamine-beta-hydroxylase but not lactate dehydrogenase. The maximal secretory responses produced by Pb2+ and Ca2+ were similar and nonadditive. Pb(2+)- and Ca(2+)-dependent releases showed a similar requirement for MgATP and were equally enhanced by protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) but not by kinase A activator 8-bromoadenosine 3',5'-cyclic monophosphate free base. The protein kinase C inhibitor staurosporine blocked the TPA-stimulated component of secretion but had no effect on the NE release in the absence of TPA. Calmidazolium, an inhibitor of calmodulin, inhibited the secretion evoked by both metals to similar extent. Agents interacting with microtubules (colchicine and vinblastine) or microfilaments (cytochalasin B and phalloidin) had no effect on secretion induced by either metal cation. These observations indicate that both Pb2+ and Ca2+ act at a common site and activate the exocytotic release of NE by an analogous mechanism. |
Databáze: | OpenAIRE |
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