Dataset Information

Calcium signalling mediated through ?7 and non-?7 nAChR stimulation is differentially regulated in bovine chromaffin cells to induce catecholamine release.

ABSTRACT:

Background and purpose

Ca(2+) signalling and exocytosis mediated by nicotinic receptor (nAChR) subtypes, especially the ?7 nAChR, in bovine chromaffin cells are still matters of debate.

Experimental approach

We have used chromaffin cell cultures loaded with Fluo-4 or transfected with aequorins directed to the cytosol or mitochondria, several nAChR agonists (nicotine, 5-iodo-A-85380, PNU282987 and choline), and the ?7 nAChR allosteric modulator PNU120596.

Key results

Minimal [Ca(2+) ](c) transients, induced by low concentrations of selective ?7 nAChR agonists and nicotine, were markedly increased by the ?7 nAChR allosteric modulator PNU120596. These potentiated responses were completely blocked by the ?7 nAChR antagonist ?-bungarotoxin (?7-modulated-response). Conversely, high concentrations of the ?7 nAChR agonists, nicotine or 5-iodo-A-85380 induced larger [Ca(2+) ](c) transients, that were blocked by mecamylamine but were unaffected by ?-bungarotoxin (non-?7 response). [Ca(2+) ](c) increases mediated by ?7 nAChR were related to Ca(2+) entry through non-L-type Ca(2+) channels, whereas non-?7 nAChR-mediated signals were related to L-type Ca(2+) channels; Ca(2+) -induced Ca(2+) -release contributed to both responses. Mitochondrial involvement in the control of [Ca(2+) ](c) transients, mediated by either receptor, was minimal. Catecholamine release coupled to ?7 nAChRs was more efficient in terms of catecholamine released/[Ca(2+) ](c) .

Conclusions and implications

[Ca(2+) ](c) and catecholamine release mediated by ?7 nAChRs required an allosteric modulator and low doses of the agonist. At higher agonist concentrations, the ?7 nAChR response was lost and the non-?7 nAChRs were activated. Catecholamine release might therefore be regulated by different nAChR subtypes, depending on agonist concentrations and the presence of allosteric modulators of ?7 nAChRs.

SUBMITTER: del Barrio L

PROVIDER: S-EPMC3012409 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Calcium signalling mediated through α7 and non-α7 nAChR stimulation is differentially regulated in bovine chromaffin cells to induce catecholamine release.

del Barrio Laura L Egea Javier J León Rafael R Romero Alejandro A Romero Alejandro A Ruiz Ana A Montero Mayte M Alvarez Javier J López Manuela G MG

British journal of pharmacology 20110101 1

<h4>Background and purpose</h4>Ca(2+) signalling and exocytosis mediated by nicotinic receptor (nAChR) subtypes, especially the α7 nAChR, in bovine chromaffin cells are still matters of debate.<h4>Experimental approach</h4>We have used chromaffin cell cultures loaded with Fluo-4 or transfected with aequorins directed to the cytosol or mitochondria, several nAChR agonists (nicotine, 5-iodo-A-85380, PNU282987 and choline), and the α7 nAChR allosteric modulator PNU120596.<h4>Key results</h4>Minimal ...[more]

PMID: 20840468

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