C-type natriuretic peptide (CNP) effects on intracellular calcium [Ca2+](i) in mouse gonadotrope-derived αT3-1 cell line

R. C. Fowkes, W. Forrest-Owen, B. Williams, C. A. McArdle

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

C-type natriuretic peptide (CNP), the third member of the atrial natriuretic peptide family, acts via guanylyl cyclase containing GC-B receptors to stimulate cyclic guanosine 3',5' monophosphate (cGMP) accumulation in the gonadotrope-derived αT3-1 cell line and rat pituitary cells. This effect is inhibited by concomitant activation of the phospholipase C (PLC)-coupled gonadotrophin hormone-releasing hormone (GnRH) receptors in these cells. Since GnRH stimulates gonadotrophin secretion from gonadotropes by increasing the cytosolic Ca2+ concentration ([Ca2+](i)) and natriuretic peptides have been found to influence PLC/Ca2+ signalling in other systems, we have investigated whether CNP can alter basal or GnRH-stimulated changes in [Ca2+](i) in αT3-1 cells. In Ca2+-containing medium, 10-7 M CNP modestly, but significantly increased [Ca2+](i) over several min, but subsequently inhibited the elevation of [Ca2+](i) in response to 10-7 M GnRH in both Ca2+-containing and Ca2+-free medium. This inhibitory effect was mimicked by 10-6 M 8-Br-cGMP, but not by ANP, indicating mediation by cyclic GMP and the CNP-specific GC-B receptor. However, basal and GnRH-stimulated inositol (1,4,5) trisphosphate (Ins(1,4,5)P3) generation were not measurably affected by CNP, and CNP failed to affect thapsigargin-induced capacitative Ca2+ entry. Thus, it appears that the cross-talk between CNP and GnRH in these cells is reciprocal in that GnRH modulates CNP effects on cGMP generation, whereas, CNP modulates GnRH effects on Ca2+ mobilisation. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalRegulatory Peptides
Volume84
Issue number1-3
DOIs
StatePublished - 22 Oct 1999
Externally publishedYes

Keywords

  • Cyclic GMP
  • GnRH
  • Intracellular signalling
  • Pituitary

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