Ca2+ mobilization by the LH receptor expressed in Xenopus oocytes independent of 3′, 5′-cyclic adenosine monophosphate formation: Evidence for parallel activation of two signaling pathways

Thomas Gudermann, Colin Nichols, Finn Olav Levy, Marie Birnbaumer, Lutz Birnbaumer

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Abstract

The cDNAs encoding the murine LH receptor (LHR) and the human β2-adrenoceptor (h β2AR) were cloned and RNAs complementary to their sense strands (cRNAs) were injected into defolliculated Xenopus oocytes. This led to expression, respectively, of LH- and isoproterenol-stimulable adenylyl cyclase activities, indicating that functionally active receptor cDNAs had been cloned. In oocytes injected with LHR cRNA, but not in control or h β2AR cRNA-injected oocytes, human CG and LH increased a Ca2+-activated Cl current, as measured by the two-microelectrode voltage-clamp method. This effect was not seen with isoproterenol in control or h β2AR cRNA-injected oocytes, it was also not observed in response to forskolin or (Bu2cAMP. The response to human CG could be obtained in the absence of extracellular Ca2+ but was abolished by injection of EGTA, indicating that it was caused by mobilization of Ca2+ from intracellular stores. The response was unaffected by overnight treatment with 1 μg/ml pertussis toxin. The experiments show that a glycoprotein hormone receptor can be expressed as a functionally active molecule in Xenopus oocytes, and that the LHR has the ability of activating two separate intracellular signaling pathways: one forming the second messenger cAMP, and the other mobilizing Ca2+ from intracellular stores. It is proposed that the latter is secondary to a primary activation of phospholipase C by the LHR, which elevates intracellular Ca2+ via intermediary elevation of inositol phosphates, presumably (1, 4, 5)inositol trisphosphate.

Original languageEnglish
Pages (from-to)272-278
Number of pages7
JournalMolecular Endocrinology
Volume6
Issue number2
DOIs
StatePublished - Feb 1 1992

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