Scientific article
Open access

Pituitary adenylate cyclase-activating polypeptide increases [Ca2]i in rat gonadotrophs through an inositol trisphosphate-dependent mechanism

Published inThe Journal of biological chemistry, vol. 269, no. 8, p. 5680-5686
Publication date1994

Pituitary adenylate cyclase-activating polypeptide (PACAP) increases cAMP production and stimulates hormone release from a variety of anterior pituitary cells. However, in anterior pituitary gonadotrophs PACAP stimulates oscillations in cytosolic free Ca2+ concentration ([Ca2+]i) that appear to be independent of cAMP. To study the mechanisms involved in this response, we used the patch-clamp technique to microperfuse various agents into single rat gonadotrophs while monitoring [Ca2+]i with microfluorometry. Extracellular application of PACAP to single gonadotrophs stimulated high amplitude (> 1 microM) oscillations in [Ca2+]i, which were blocked by intracellular application of GDP beta S (guanosine 5'-O-2-thiodiphosphate), indicating the involvement of a G-protein. To identify the intracellular messenger(s) involved, we microperfused gonadotrophs with cAMP, inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), or heparin, an antagonist of the Ins(1,4,5)P3 receptor. A high concentration of cAMP (100 microM) had no significant effect on basal [Ca2+]i and did not alter the PACAP-stimulated Ca2+ response. Heparin, but not its inactive isoform, completely blocked the PACAP-stimulated increase in [Ca2+]i, while Ins(1,4,5)P3 stimulated oscillations in [Ca2+]i very similar to those observed in response to PACAP. These results strongly suggest that PACAP mobilizes Ca2+ through an Ins(1,4,5)P3-dependent mechanism. The fact that PACAP stimulates two signaling pathways in pituitary cells could substantially enhance the signaling potential of this hypothalamic peptide.

  • Animals
  • Calcium/metabolism
  • Cells, Cultured
  • Cyclic AMP/metabolism
  • GTP-Binding Proteins/metabolism
  • Inositol 1,4,5-Trisphosphate/metabolism
  • Male
  • Neuropeptides/antagonists & inhibitors/physiology
  • Neurotransmitter Agents/antagonists & inhibitors/physiology
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Pituitary Gland, Anterior/cytology/drug effects/metabolism
  • Rats
  • Rats, Sprague-Dawley
Citation (ISO format)
RAWLINGS, Stephen Roy, DEMAUREX, Nicolas, SCHLEGEL, Werner. Pituitary adenylate cyclase-activating polypeptide increases [Ca2]i in rat gonadotrophs through an inositol trisphosphate-dependent mechanism. In: The Journal of biological chemistry, 1994, vol. 269, n° 8, p. 5680–5686.
Main files (1)
Article (Published version)
ISSN of the journal0021-9258

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