Effects of Extracellular Nucleotides in the Pituitary: Adenosine Triphosphate Receptor-Mediated Intracellular Responses in Gonadotrope-Derived αT3-1 Cells

Zhen Ping Chen, Martin Kratzmeier, Annette Poch, Su Xu, Craig A. Mcardle, Andrew Levy, Amal K. Mukhopadhyay, Stafford L. Lightman

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34 Scopus citations

Abstract

We have recently identified gonadotropes as target cells for ATP action via ATP receptors of the P2U subtype. The present studies have used gonadotrope-derived αT3-1 cells to examine the possible signaling mechanisms subserving ATP action in gonadotropes. Addition of ATP produced a biphasic intracellular Ca2+ (Ca2+i) response: a transient spike followed by a small plateau. Removal of extracellular Ca2+ or depolarization with KCl abolished the plateau but had no effect on the spike. The plateau was also blocked by cadmium or nifedipine but not nickel. Pretreatment with GnRH or thapsigargin but not ryanodine inhibited the subsequent Ca2+i response to ATP. Pertussis toxin had no effect on ATP-induced Ca2+i response, whereas the phospholipase C inhibitor U73122 reduced the response. These observations suggest that the Ca2+i response is mediated by a pertussis toxin-insensitive and phospholipase C-coupled G-protein and reflects Ca2+ release from the GnRH- and thapsigargin-sensitive Ca2+ pool followed by Ca2+ influx through high voltage-gated Ca2+ channels. Activation of these ATP receptors had no apparent effects on the cAMP and cGMP signaling systems. Treatment with ATPγS caused the translocation of protein kinase C (PKC)∈ but not PKCζ and PKCα to the particulate fraction. These data not only characterize the ATP receptor-mediated intracellular signaling in αT3-1 cells and render further evidence for a mediator role for nucleotides in gonadotrope function but also provide the first direct demonstration of PKC translocation by ATP receptors.

Original languageEnglish
Pages (from-to)248-256
Number of pages9
JournalEndocrinology
Volume137
Issue number1
DOIs
StatePublished - 1996
Externally publishedYes

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