In A7r5 cells with empty intracellular Ca2+ stores in which the cytosolic free Ca2+ concentration ([Ca2+]i) had been increased by capacitative Ca2+ entry, stimulation of receptors linked to phospholipase C (PLC), including those for Arg8-vasopressin (AVP) and platelet-derived growth factor (PDGF), caused a decrease in [Ca2+]i. This effect was further examined in a stable variant of the A7r5 cell line in which the usual ability of hormones to stimulate non-capacitative Ca2+ entry is not expresssed. In thapsigargin-treated cells, neither AVP nor PDGF affected capacitative Mn2+ or Ba2+ entry, but both stimulated the rate of Ca2+ extrusion, and their abilities to decrease [Ca2+]i were only partially inhibited by removal of extracellular Na+. These results suggest that receptors linked to PLC also stimulate plasma membrane Ca2+ pumps. Activation of protein kinase C by phorbol 12,13-dibutyrate (PDBu, 1 μM) also caused a decrease in [Ca2+]i by accelerating Ca2+ removal from the cytosol; the effect was again only partially inhibited by removal of extracellular Na+. An inhibitor of PKC, Ro31-8220 (10 μM), abolished the ability of PDBu to decrease [Ca2+]i,without affecting the response to maximal or submaximal concentrations of AVP. Similar experiments with PDGF were impracticable because Ro31-8220, presumably by inhibiting the tyrosine kinase activity of the PDGF receptor, abolished all responses to PDGF. U73122 (10 μM), an inhibitor of PLC, completely inhibited PDGF- or AVP-evoked Ca2+ mobilization, without preventing either stimulus from causing a decrease in [Ca2+]i. We conclude that receptors coupled to PLC, whether via G-proteins or protein tyrosine kinase activity, also share an ability to stimulate the plasma membrane Ca2+ pump via a mechanism that does not require PLC activity.
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Research Article|
August 10 1999
Receptors linked to polyphosphoinositide hydrolysis stimulate Ca2+ extrusion by a phospholipase C-independent mechanism
Lisa M. BROAD;
Lisa M. BROAD
1Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, U.K.
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Toby R. CANNON;
Toby R. CANNON
1Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, U.K.
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Alison D. SHORT;
Alison D. SHORT
1Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, U.K.
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Colin W. TAYLOR
Colin W. TAYLOR
1
1Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, U.K.
1To whom correspondence should be addressed (e-mail cwt1000@cam.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 04 1999
Revision Received:
May 12 1999
Accepted:
June 21 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 342 (1): 199–206.
Article history
Received:
March 04 1999
Revision Received:
May 12 1999
Accepted:
June 21 1999
Citation
Lisa M. BROAD, Toby R. CANNON, Alison D. SHORT, Colin W. TAYLOR; Receptors linked to polyphosphoinositide hydrolysis stimulate Ca2+ extrusion by a phospholipase C-independent mechanism. Biochem J 15 August 1999; 342 (1): 199–206. doi: https://doi.org/10.1042/bj3420199
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