+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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

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

Endocrinology 137(1): 248-256

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.

(PDF emailed within 0-6 h: $19.90)

Accession: 045910098

Download citation: RISBibTeXText

PMID: 8536620

DOI: 10.1210/endo.137.1.8536620

Related references

Extracellular adenosine triphosphate activates phospholipase C and mobilizes intracellular calcium in primary cultures of sheep anterior pituitary cells. Febs Letters 243(2): 333-336, 1989

Lysis of human monocytic leukemia cells by extracellular adenosine triphosphate: mechanism and characterization of the adenosine triphosphate receptor. Blood 82(5): 1578-1585, 1993

Pituitary adenylate cyclase-activating polypeptide and cyclic adenosine 3',5'-monophosphate stimulate the promoter activity of the rat gonadotropin-releasing hormone receptor gene via a bipartite response element in gonadotrope-derived cells. Journal of Biological Chemistry 276(26): 23562-23571, 2001

Effects of pituitary adenylate cyclase-activating polypeptide in the pituitary: activation of two signal transduction pathways in the gonadotrope-derived alpha T3-1 cell line. Endocrinology 134(1): 315-323, 1994

Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, inhibits muscarinic acetylcholine receptor-mediated activation of extracellular signal-regulated kinases in PC12 cells. Anesthesia and Analgesia 107(6): 1892-1898, 2008

Intracellular and extracellular adenosine triphosphate in regulation of insulin secretion from pancreatic β cells (β). Journal of Diabetes 6(2): 113-119, 2014

The intracellular distribution of free nucleotides in the tobacco leaf. Formation of adenosine 5'-phosphate from adenosine 5'-triphosphate in the chloroplasts. Biochemical Journal 108(1): 1-8, 1968

Effects of extracellular adenosine triphosphate and adenosine on apoptosis of TE-13 esophageal carcinoma cells. Zhongguo Yaolixue Yu Dulixue Zazhi 18(2): 124-126, 2004

Distinct intracellular Ca2+ response to extracellular adenosine triphosphate in pancreatic beta-cells in rats and mice. Endocrine 22(3): 185-192, 2004

Pharmacological analysis of calcium responses mediated by the human A3 adenosine receptor in monocyte-derived dendritic cells and recombinant cells. Molecular Pharmacology 63(2): 342-350, 2003

Effects of extracellular nucleotides in the thyroid: P2Y2 receptor-mediated ERK1/2 activation and c-Fos induction in PC Cl3 cells. Cellular Signalling 17(6): 739-749, 2005

Selective regulation of G protein-coupled receptor-mediated signaling by G protein-coupled receptor kinase 2 in FRTL-5 cells: analysis of thyrotropin, alpha(1B)-adrenergic, and A(1) adenosine receptor-mediated responses. Molecular Pharmacology 56(2): 316-324, 1999

Extracellular Uridine Triphosphate and Adenosine Triphosphate Attenuate Endothelial Inflammation through miR-22-Mediated ICAM-1 Inhibition. Journal of Vascular Research 52(2): 71-80, 2015

Role of extracellular adenosine triphosphate in the cytotoxic T-lymphocyte-mediated lysis of antigen presenting cells. Blood 85(11): 3173-3182, 1995

Extracellular adenosine-5'-triphosphate increases intracellular calcium concentration of the rabbit eye suprachoroid via activation of the intracellular signal transduction. Nippon Ganka Gakkai Zasshi 98(1): 69-74, 1994