Effects of extracellular nucleotides in the pituitary: adenosine triphosphate receptor-mediated intracellular responses in gonadotrope-derived alpha T3-1 cells.

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 alpha T3-1 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 ATP-gamma S caused the translocation of protein kinase C (PKC) epsilon but not PKC zeta and PKC alpha to the particulate fraction. These data not only characterize the ATP receptor-mediated intracellular signaling in alpha T3-1 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.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Chen ZP,Kratzmeier M,Poch A,Xu S,McArdle CA,Levy A,Mukhopadhyay AK,Lightman SL

doi

10.1210/endo.137.1.8536620

subject

Has Abstract

pub_date

1996-01-01 00:00:00

pages

248-56

issue

1

eissn

0013-7227

issn

1945-7170

journal_volume

137

pub_type

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