Abstract
Exocytosis proceeds by either full fusion or 'kiss-and-run' between vesicle and plasma membrane. Switching between these two modes permits the cell to regulate the kinetics and amount of secretion. Here we show that ATP receptor activation reduces secretion downstream from cytosolic Ca2+ elevation in rat adrenal chromaffin cells. This reduction is mediated by activation of a pertussis toxin-sensitive G(i/o) protein, leading to activation of G(betagamma) subunits, which promote the 'kiss-and-run' mode by reducing the total open time of the fusion pore during a vesicle fusion event. Furthermore, parallel activation of the muscarinic acetylcholine receptor removes the inhibitory effects of ATP on secretion. This is mediated by a G(q) pathway through protein kinase C activation. The inhibitory effects of ATP and its reversal by protein kinase C activation are also shared by opioids and somatostatin. Thus, a variety of G protein pathways exist to modulate Ca2+-evoked secretion at specific steps in fusion pore formation.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / drug effects
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Action Potentials / physiology
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Action Potentials / radiation effects
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / pharmacology
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Adrenal Medulla / cytology
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Analgesics, Opioid / pharmacology
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Animals
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Calcium / metabolism
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Cells, Cultured
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Chromaffin Cells / drug effects
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Chromaffin Cells / metabolism*
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Dose-Response Relationship, Radiation
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Drug Interactions
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Dynamins / pharmacology
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Electric Stimulation / methods
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Electrochemistry / methods
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Enzyme Inhibitors / pharmacology
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GTP-Binding Protein beta Subunits / metabolism*
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GTP-Binding Protein beta Subunits / pharmacology
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GTP-Binding Protein gamma Subunits / metabolism*
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Ionomycin / pharmacology
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Ionophores / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / radiation effects
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Muscarine / pharmacology
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Neural Inhibition / drug effects
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Neural Inhibition / physiology
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Patch-Clamp Techniques / methods
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Pertussis Toxin / pharmacology
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Potassium Chloride / pharmacology
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Protein Kinase C / metabolism*
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Protein Kinases / pharmacology
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Rats
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Receptors, G-Protein-Coupled / metabolism*
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Recombinant Fusion Proteins / pharmacology
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Somatostatin / pharmacology
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Thionucleotides / pharmacology
Substances
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Analgesics, Opioid
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Enzyme Inhibitors
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GTP-Binding Protein beta Subunits
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GTP-Binding Protein gamma Subunits
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Ionophores
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Receptors, G-Protein-Coupled
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Recombinant Fusion Proteins
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Thionucleotides
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Somatostatin
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Ionomycin
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Potassium Chloride
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Muscarine
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Adenosine Triphosphate
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Pertussis Toxin
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Protein Kinases
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Protein Kinase C
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Dynamins
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Calcium
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2-methylthio-ATP