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

Published in The Journal of biological chemistry. 1994, vol. 269, no. 8, p. 5680-6
Abstract 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.
Keywords AnimalsCalcium/metabolismCells, CulturedCyclic AMP/metabolismGTP-Binding Proteins/metabolismInositol 1,4,5-Trisphosphate/metabolismMaleNeuropeptides/antagonists & inhibitors/physiologyNeurotransmitter Agents/antagonists & inhibitors/physiologyPituitary Adenylate Cyclase-Activating PolypeptidePituitary Gland, Anterior/cytology/drug effects/metabolismRatsRats, Sprague-Dawley
PMID: 7907085
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Research group Signaux intracellulaires (210)
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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. 5680-6. https://archive-ouverte.unige.ch/unige:30335

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Deposited on : 2013-10-11

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