ACTH stimulates the release of alkaline phosphatase through Gi-mediated activation of a phospholipase C and the release of inositolphosphoglycan
We have previously reported that ACTH activates a phospholipase C that hydrolyzes glycosylphosphatidylinositol (GPI), which would release inositolphosphoglycan (IPG) to the extracellular medium, and that an IPG purified from Trypanosoma cruzi is able to inhibit ACTH-mediated steroid production in ad...
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2004
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v258_n1-2_p191_Martini http://hdl.handle.net/20.500.12110/paper_03008177_v258_n1-2_p191_Martini |
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paper:paper_03008177_v258_n1-2_p191_Martini2023-06-08T15:27:25Z ACTH stimulates the release of alkaline phosphatase through Gi-mediated activation of a phospholipase C and the release of inositolphosphoglycan ACTH Alkaline phosphate Gi Glycosylphosphatidylinositol (GPI) Phospholipase C Steroid biosynthesis 1 [[6 (3 methoxyestra 1,3,5(10) trien 17beta yl)amino]hexyl] 1h pyrrole 2,5 dione alkaline phosphatase antibody bucladesine corticosterone corticotropin cyclic AMP glycan derivative glycosylphosphatidylinositol guanine nucleotide binding protein inhibitory guanine nucleotide binding protein inositol phosphate pertussis toxin phospholipase C phospholipase C inhibitor sodium chloride triton x 114 adrenal cortex cell animal cell article cell culture controlled study culture medium enzyme activation enzyme release extracellular fluid hormone inhibition hormone synthesis male nonhuman phase partitioning phospholipid synthesis phospholipid transfer protein function rat Adrenal Glands Adrenocorticotropic Hormone Alkaline Phosphatase Animals Bucladesine Cells, Cultured Enzyme Activation Enzyme Inhibitors Glycosylphosphatidylinositols GTP-Binding Protein alpha Subunit, Gi2 GTP-Binding Protein alpha Subunits, Gi-Go Inositol Phosphates Male Oligosaccharides Phospholipase C Polysaccharides Proto-Oncogene Proteins Rats Rats, Sprague-Dawley Signal Transduction Trypanosoma Trypanosoma cruzi We have previously reported that ACTH activates a phospholipase C that hydrolyzes glycosylphosphatidylinositol (GPI), which would release inositolphosphoglycan (IPG) to the extracellular medium, and that an IPG purified from Trypanosoma cruzi is able to inhibit ACTH-mediated steroid production in adrenocortical cells. In the present paper, it was found that anti-inositolphosphoglycan antibodies (anti-CRD) increased ACTH-mediated corticosterone production, which indicates that an endogenous IPG is a physiological inhibitor of ACTH response. On the other hand, we investigated the release to the extracellular medium of the GPI-anchored enzyme, alkaline phosphatase, by ACTH. We found that: (a) the released enzyme appeared in the aqueous phase after Triton X-114 partitioning, consistent with loss of the GPI, (b) the phospholipase C inhibitor, U73122, impaired the release of the enzyme by the hormone and (c) two inhibitors of IPG uptake, inositol 2-monophosphate and 2 M NaCl, increased the amount of alkaline phosphatase in the extracellular medium. These results suggest that ACTH releases alkaline phosphatase by activation of a phospholipase C. Dibutyryladenosine-3′,5′-cyclic monophosphate (db-cAMP) was able to increase the release of alkaline phosphatase from adrenocortical cells and this effect was inhibited by U73122, suggesting that cAMP is involved in the activation of phospholipase C. In addition, it was found that a pertussis-toxin sensitive G-protein is required for ACTH- and db-cAMP-mediated release of alkaline phosphatase and that incorporation of anti-Gi antibodies in adrenocortical cells inhibited the release of alkaline phosphatase by ACTH. Our results suggest that ACTH increases the release of alkaline phosphatase by activation of a phospholipase C through cAMP and Gi which would contribute to produce IPG. It was also found that the two inhibitors of IPG uptake, inositol-2-monophosphate and 2 M NaCl, increased the amount of alkaline phosphatase in the extracellular medium of ACTH-treated cells more than in control cells, indicating that ACTH also stimulates the uptake of IPG. These data support a role of GPI and the involvement of Gi in ACTH action. © 2004 Kluwer Academic Publishers. 2004 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v258_n1-2_p191_Martini http://hdl.handle.net/20.500.12110/paper_03008177_v258_n1-2_p191_Martini |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
ACTH Alkaline phosphate Gi Glycosylphosphatidylinositol (GPI) Phospholipase C Steroid biosynthesis 1 [[6 (3 methoxyestra 1,3,5(10) trien 17beta yl)amino]hexyl] 1h pyrrole 2,5 dione alkaline phosphatase antibody bucladesine corticosterone corticotropin cyclic AMP glycan derivative glycosylphosphatidylinositol guanine nucleotide binding protein inhibitory guanine nucleotide binding protein inositol phosphate pertussis toxin phospholipase C phospholipase C inhibitor sodium chloride triton x 114 adrenal cortex cell animal cell article cell culture controlled study culture medium enzyme activation enzyme release extracellular fluid hormone inhibition hormone synthesis male nonhuman phase partitioning phospholipid synthesis phospholipid transfer protein function rat Adrenal Glands Adrenocorticotropic Hormone Alkaline Phosphatase Animals Bucladesine Cells, Cultured Enzyme Activation Enzyme Inhibitors Glycosylphosphatidylinositols GTP-Binding Protein alpha Subunit, Gi2 GTP-Binding Protein alpha Subunits, Gi-Go Inositol Phosphates Male Oligosaccharides Phospholipase C Polysaccharides Proto-Oncogene Proteins Rats Rats, Sprague-Dawley Signal Transduction Trypanosoma Trypanosoma cruzi |
| spellingShingle |
ACTH Alkaline phosphate Gi Glycosylphosphatidylinositol (GPI) Phospholipase C Steroid biosynthesis 1 [[6 (3 methoxyestra 1,3,5(10) trien 17beta yl)amino]hexyl] 1h pyrrole 2,5 dione alkaline phosphatase antibody bucladesine corticosterone corticotropin cyclic AMP glycan derivative glycosylphosphatidylinositol guanine nucleotide binding protein inhibitory guanine nucleotide binding protein inositol phosphate pertussis toxin phospholipase C phospholipase C inhibitor sodium chloride triton x 114 adrenal cortex cell animal cell article cell culture controlled study culture medium enzyme activation enzyme release extracellular fluid hormone inhibition hormone synthesis male nonhuman phase partitioning phospholipid synthesis phospholipid transfer protein function rat Adrenal Glands Adrenocorticotropic Hormone Alkaline Phosphatase Animals Bucladesine Cells, Cultured Enzyme Activation Enzyme Inhibitors Glycosylphosphatidylinositols GTP-Binding Protein alpha Subunit, Gi2 GTP-Binding Protein alpha Subunits, Gi-Go Inositol Phosphates Male Oligosaccharides Phospholipase C Polysaccharides Proto-Oncogene Proteins Rats Rats, Sprague-Dawley Signal Transduction Trypanosoma Trypanosoma cruzi ACTH stimulates the release of alkaline phosphatase through Gi-mediated activation of a phospholipase C and the release of inositolphosphoglycan |
| topic_facet |
ACTH Alkaline phosphate Gi Glycosylphosphatidylinositol (GPI) Phospholipase C Steroid biosynthesis 1 [[6 (3 methoxyestra 1,3,5(10) trien 17beta yl)amino]hexyl] 1h pyrrole 2,5 dione alkaline phosphatase antibody bucladesine corticosterone corticotropin cyclic AMP glycan derivative glycosylphosphatidylinositol guanine nucleotide binding protein inhibitory guanine nucleotide binding protein inositol phosphate pertussis toxin phospholipase C phospholipase C inhibitor sodium chloride triton x 114 adrenal cortex cell animal cell article cell culture controlled study culture medium enzyme activation enzyme release extracellular fluid hormone inhibition hormone synthesis male nonhuman phase partitioning phospholipid synthesis phospholipid transfer protein function rat Adrenal Glands Adrenocorticotropic Hormone Alkaline Phosphatase Animals Bucladesine Cells, Cultured Enzyme Activation Enzyme Inhibitors Glycosylphosphatidylinositols GTP-Binding Protein alpha Subunit, Gi2 GTP-Binding Protein alpha Subunits, Gi-Go Inositol Phosphates Male Oligosaccharides Phospholipase C Polysaccharides Proto-Oncogene Proteins Rats Rats, Sprague-Dawley Signal Transduction Trypanosoma Trypanosoma cruzi |
| description |
We have previously reported that ACTH activates a phospholipase C that hydrolyzes glycosylphosphatidylinositol (GPI), which would release inositolphosphoglycan (IPG) to the extracellular medium, and that an IPG purified from Trypanosoma cruzi is able to inhibit ACTH-mediated steroid production in adrenocortical cells. In the present paper, it was found that anti-inositolphosphoglycan antibodies (anti-CRD) increased ACTH-mediated corticosterone production, which indicates that an endogenous IPG is a physiological inhibitor of ACTH response. On the other hand, we investigated the release to the extracellular medium of the GPI-anchored enzyme, alkaline phosphatase, by ACTH. We found that: (a) the released enzyme appeared in the aqueous phase after Triton X-114 partitioning, consistent with loss of the GPI, (b) the phospholipase C inhibitor, U73122, impaired the release of the enzyme by the hormone and (c) two inhibitors of IPG uptake, inositol 2-monophosphate and 2 M NaCl, increased the amount of alkaline phosphatase in the extracellular medium. These results suggest that ACTH releases alkaline phosphatase by activation of a phospholipase C. Dibutyryladenosine-3′,5′-cyclic monophosphate (db-cAMP) was able to increase the release of alkaline phosphatase from adrenocortical cells and this effect was inhibited by U73122, suggesting that cAMP is involved in the activation of phospholipase C. In addition, it was found that a pertussis-toxin sensitive G-protein is required for ACTH- and db-cAMP-mediated release of alkaline phosphatase and that incorporation of anti-Gi antibodies in adrenocortical cells inhibited the release of alkaline phosphatase by ACTH. Our results suggest that ACTH increases the release of alkaline phosphatase by activation of a phospholipase C through cAMP and Gi which would contribute to produce IPG. It was also found that the two inhibitors of IPG uptake, inositol-2-monophosphate and 2 M NaCl, increased the amount of alkaline phosphatase in the extracellular medium of ACTH-treated cells more than in control cells, indicating that ACTH also stimulates the uptake of IPG. These data support a role of GPI and the involvement of Gi in ACTH action. © 2004 Kluwer Academic Publishers. |
| title |
ACTH stimulates the release of alkaline phosphatase through Gi-mediated activation of a phospholipase C and the release of inositolphosphoglycan |
| title_short |
ACTH stimulates the release of alkaline phosphatase through Gi-mediated activation of a phospholipase C and the release of inositolphosphoglycan |
| title_full |
ACTH stimulates the release of alkaline phosphatase through Gi-mediated activation of a phospholipase C and the release of inositolphosphoglycan |
| title_fullStr |
ACTH stimulates the release of alkaline phosphatase through Gi-mediated activation of a phospholipase C and the release of inositolphosphoglycan |
| title_full_unstemmed |
ACTH stimulates the release of alkaline phosphatase through Gi-mediated activation of a phospholipase C and the release of inositolphosphoglycan |
| title_sort |
acth stimulates the release of alkaline phosphatase through gi-mediated activation of a phospholipase c and the release of inositolphosphoglycan |
| publishDate |
2004 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03008177_v258_n1-2_p191_Martini http://hdl.handle.net/20.500.12110/paper_03008177_v258_n1-2_p191_Martini |
| _version_ |
1768544728898338816 |