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Multiple P2 receptors contribute to a transient increase in intracellular Ca2+ concentration in ATP-stimulated rat brown adipocytes

Published online by Cambridge University Press:  31 October 2002

Mariko Omatsu-Kanbe*
Affiliation:
Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
Takahiro Isono
Affiliation:
Department of Central Research Laboratory, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
Hiroshi Matsuura
Affiliation:
Department of Physiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
*
Corresponding author: m_omatsu@belle.shiga-med.ac.jp
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Abstract

Extracellular ATP in micromolar concentrations evokes a transient elevation in intracellular free Ca2+ concentration ([Ca2+]i), which arises primarily from a release of Ca2+ from intracellular stores in rat brown adipocytes. We investigated the mechanisms underlying this transient nature of [Ca2+]i elevation during exposure to ATP by using fura-2 fluorescence measurements together with the P2 receptor antagonists pyridoxal-phosphate-6-azophenyl-2’,4’-disulfonic acid (PPADS) and suramin. Extracellular ATP (10 µM) almost completely depressed the thapsigargin (100 nM)-evoked [Ca2+]i elevation mediated through storeoperated Ca2+ entry. The inhibitory effect of ATP was antagonized by PPADS with IC50 of 0.7 µM. In the presence of PPADS at concentrations of more than 5 µM, the ATP-induced [Ca2+]i elevation became sustained during the entire duration of the agonist application, although the magnitude of the sustained [Ca2+]i elevation was reduced in a concentration-dependent manner by PPADS with an IC50 of 200 µM. In contrast, the ATPinduced [Ca2+]i elevation was blocked by suramin in a concentration range similar to that required to antagonize the inhibitory effect of ATP on the store-operated pathway. These results suggest that the [Ca2+]i responses to extracellular ATP in rat brown adipocytes are mediated through the activation of at least two distinct P2 receptors exhibiting different sensitivities to PPADS but similar sensitivities to suramin. Extracellular ATP stimulates the PPADS-resistant P2 receptor to mobilize intracellular Ca2+ stores, which is probably followed by the activation of store-operated Ca2+ entry. Extracellular ATP, however, would inhibit this Ca2+ entry process through the stimulation of the PPADS-sensitive P2-receptor, which may underlie the transient nature of [Ca2+]i elevation in response to extracellular ATP.

Type
Research Article
Copyright
Copyright © Experimental Physiology 2002

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