Neurotransmitter release from bradykinin-stimulated PC12 cells. Stimulation of cytosolic calcium and neurotransmitter release.
The effect of bradykinin on intracellular free Ca2+ and neurotransmitter secretion was investigated in the rat pheochromocytoma cell line PC12. Bradykinin was shown to induce a rapid, but transient, increase in intracellular free Ca2+ which could be separated into an intracellular Ca2+ release component and an extracellular Ca2+ influx component. The bradykinin-induced stimulation of intracellular free Ca2+ displayed a similar time course, concentration dependencies and extracellular Ca2+ dependence as that found for neurotransmitter release, indicating an association between intracellular free Ca2+ levels and neurotransmitter secretion. The selective BK1-receptor antagonist des-Arg9,[Leu8]BK (where BK is bradykinin) did not significantly affect the stimulation of intracellular free Ca2+ or neurotransmitter release. In contrast, these effects of bradykinin were effectively blocked by the selective BK2-receptor antagonist [Thi5,8,D-Phe7]BK, and mimicked by the BK2 partial agonist [D-Phe7]BK in a concentration-dependent manner. The stimulation of intracellular free Ca2+ and neurotransmitter release induced by bradykinin was shown not to involve voltage-sensitive Ca2+ channels, since calcium antagonists had no effect on either response at concentrations which effectively inhibit depolarization-induced responses. These results indicate that bradykinin, acting through the interaction with the BK2 receptor, stimulates an increase in intracellular free Ca2+ leading to neurotransmitter secretion. Furthermore, bradykinin-induced responses involve the release of intracellular Ca2+ and the influx of extracellular Ca2+ that is not associated with the activation of voltage-sensitive Ca2+ channels.
Appell
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Department of Molecular Biology, A. H. Robins Research Laboratories, Richmond, VA 23220.
Barefoot
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DS
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D015544:Inositol 1,4,5-Trisphosphate; D004110:Diltiazem; D001920:Bradykinin; D002118:Calcium; D004298:Dopamine