Activation of different pathways for calcium elevation by bradykinin and ATP in rat pheochromocytoma (PC 12) cells.
We have studied the pathways by which extracellular bradykinin and adenosine 5'-triphosphate (ATP) elicit changes in intracellular free calcium ([Ca2+]i) in nerve-growth-factor(NGF)- treated rat pheochromocytoma (PC 12) cells. Both substances caused a significant rise in [Ca2+]i as assessed by fura-2 based microfluorimetry. The bradykinin-induced response consisted of an initial Ca2+ mobilization from an internal pool followed by a sustained increase in [Ca2+]i, which was due to activation of a small inward current. The initial response always started at a localized site opposite to the cell nucleus. The inward current was partially carried by Ca2+ and began with a time lag of about 4 s after the start of the initial transient signal. Stepwise hyperpolarization of the plasma membrane, after activation of the inward current by bradykinin, caused a simultaneous increase in current amplitude and in [Ca2+]i, due to an increase in the driving force for Ca2+ influx. With ATP as an agonist the onset of inward current coincided with an increase in [Ca2+]i. Inward current and [Ca2+]i were enhanced during hyperpolarizing steps indicating a substantial Ca2+ influx through ATP-activated channels. No release of Ca2+ from internal stores, but a large Na+ inward current, was observed in Ca(2+)-free external solution after addition of ATP. While the bradykinin-induced responses were much more pronounced in cell bodies than in growth cones, the ATP effects were somewhat variable in cell bodies and more homogeneous in growth cones.
Reber
B F
BF
Department of Pharmacology, University of Berne, Switzerland.
Neuhaus
R
R
Reuter
H
H
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats
D009414:Nerve Growth Factors; D000255:Adenosine Triphosphate; D001920:Bradykinin; D002118:Calcium