An inositol phosphoglycan from Trypanosoma cruzi inhibits ACTH action in calf adrenocortical cells.
We describe the effect of an inositol phosphoglycan (IPG) purified from Trypanosoma cruzi on the stimulation of aldosterone and cAMP production by ACTH in calf adrenocortical cells. T. cruzi IPG has two galactofuranose residues (Galf) which are not frequent in other IPGs. The effect of IPG with galactofuranose residues (IPG Galf) and IPG without these residues (IPG) was investigated. It was found that IPG Galf slightly decreased the stimulation of aldosterone and cAMP production by ACTH, whereas IPG significantly inhibited ACTH-mediated accumulation of both aldosterone and cAMP. The inhibition of aldosterone content in ACTH-treated cells by IPG was dose dependent. It was also found that the pretreatment of calf adrenocortical cells with IPG inhibited the accumulation of aldosterone provoked by ACTH and dibutyryladenosine-3',5'-cyclic monophosphate (db-cAMP). On the other hand, the activation of a GPI (glycosyl phosphatidylinositol)-phospholipase C by ACTH was evaluated. First it was found that the release of ceramide from a GPI-like molecule: a glycoinositol-phosphoceramide (LPPG) purified from T. cruzi is increased in ACTH-treated cells. Second, the release of alkaline phosphatase, a GPI-anchored enzyme, to the extracellular medium was increased in these cells by ACTH. These data suggest that ACTH activates a phospholipase C in calf adrenocortical cells, releasing IPG, which in turn may inhibit, or modulate ACTH action.
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
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MC
Vila
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Cozza
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C
Lima
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MI
Ramirez
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De Lederkremer
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006028:Glycosphingolipids / Q000737:chemistry; D006727:Hormone Antagonists / Q000302:isolation & purification / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008969:Molecular Sequence Data; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000737:chemistry*; D010738:Type C Phospholipases / Q000378:metabolism
D006028:Glycosphingolipids; D006727:Hormone Antagonists; D007295:Inositol Phosphates; D011134:Polysaccharides; C028039:inositol phosphate glycan; C008290:lipophosphonoglycan; D000450:Aldosterone; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase