Human growth hormone increases cytosolic free calcium in cultured human IM-9 lymphocytes: a novel mechanism of growth hormone transmembrane signalling.
Cytosolic free calcium ions concentration ([Ca2+]i) was measured in cell suspensions of cultured human IM-9 lymphocytes by dual wavelength fluorescence spectrometry using the calcium probe fura-2. Human GH (0.2-50 nM) induced a slow, progressive and sustained increase in [Ca2+]i. The GH effect was specific and exhibited a biphasic pattern, presumably reflecting GH receptor dimerization, typical of some other GH actions. The hGH effect depended on extracellular calcium, suggesting that at least part of the [Ca2+]i increase was due to a stimulation of calcium influx. GH did not increase IP3. Somatostatin-14 in the range 10(-10) to 10(-8) M, while having no effect of its own on [Ca2+]i, inhibited the effect of hGH. This inhibition by somatostatin was prevented by pretreatment of the cells with pertussis toxin. The hGH-induced [Ca2+]i increase was not related to either protein tyrosine phosphorylation or protein kinase C activation, thus suggesting a novel mechanism of GH transmembrane signalling.
Hagedorn Research Institute, Gentofte, Denmark.
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Ilondo
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De Meyts
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Bouchelouche
D000470:Alkaloids / Q000494:pharmacology; D016227:Benzoquinones; D002118:Calcium / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D047029:Lactams, Macrocyclic; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects*; D019311:Staurosporine; D020032:Tyrphostins
D000470:Alkaloids; D016227:Benzoquinones; D002396:Catechols; D007328:Insulin; D047029:Lactams, Macrocyclic; D009570:Nitriles; D011809:Quinones; D020032:Tyrphostins; C060152:tyrphostin 47; D017828:Rifabutin; D007334:Insulin-Like Growth Factor I; C020754:herbimycin; D015544:Inositol 1,4,5-Trisphosphate; D013006:Growth Hormone; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine; D002118:Calcium