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drug-mediated growth inhibition. 2. This was not so for APPR, to which most strains were transitory insensitive except two which were clearly sensitive. 3. AII these pyrazolopyrimidines blocked trypomastigote-amastigote transformation. 4. Incubation of pyrazolopyrimidine-insensitive wild strains with [3HIFoA, [3H]FoB and [~4C]APPR respectively indicates that insensitive cells can only accumulate low concentrations of phosphorylated metabolites. 5. This is due to a defective or impaired pyrazolopyrimidine riboside transport system in the wild type insensitive cells, as we did not detect significant variations in the levels of the various nucleoside and nucleobase metabolism enzymes studied. 6. Additional experiments suggested that FoA and FoB are incorporated by different nucleoside transport systems, as Y and ES strains were FoA-insensitive but FoB-sensitive. 7. Epimastigotes of the same T. cruzi strains were highly sensitive to low concentrations of the three pyrazoIopyrimidine ribosides studied. However, when this parasitic form was allowed to transform into trypomastigotes, these cells showed the same pyrazolopyrimidine sensitivity found before, suggesting that in T. cruzi pyrazolopyrimidine ribosideqnsensitivity is a parasite-stage specific and reversible biochemical characteristic.","publication_date":"1987,,","publication_name":"Comparative Biochemistry and Physiology Part B: Comparative Biochemistry","grobid_abstract_attachment_id":"80191831"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Defective transport of pyrazolopyrimidine ribosides in insensitive trypanosoma cruzi wild strains is a parasite-stage specific and reversible characteristic","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [16621441]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; 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if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">By using freshly isolated blood trypomastigotes of twelve 7". cruzi wild type strains we have found eight strains sensitive to FoB and FoA, while four and one were FoA-and FoB-insensitive respectiveiy to the drug-mediated growth inhibition. 2. This was not so for APPR, to which most strains were transitory insensitive except two which were clearly sensitive. 3. AII these pyrazolopyrimidines blocked trypomastigote-amastigote transformation. 4. Incubation of pyrazolopyrimidine-insensitive wild strains with [3HIFoA, [3H]FoB and [~4C]APPR respectively indicates that insensitive cells can only accumulate low concentrations of phosphorylated metabolites. 5. This is due to a defective or impaired pyrazolopyrimidine riboside transport system in the wild type insensitive cells, as we did not detect significant variations in the levels of the various nucleoside and nucleobase metabolism enzymes studied. 6. Additional experiments suggested that FoA and FoB are incorporated by different nucleoside transport systems, as Y and ES strains were FoA-insensitive but FoB-sensitive. 7. Epimastigotes of the same T. cruzi strains were highly sensitive to low concentrations of the three pyrazoIopyrimidine ribosides studied. However, when this parasitic form was allowed to transform into trypomastigotes, these cells showed the same pyrazolopyrimidine sensitivity found before, suggesting that in T. cruzi pyrazolopyrimidine ribosideqnsensitivity is a parasite-stage specific and reversible biochemical characteristic.</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":80191831,"attachmentType":"pdf","workUrl":"https://www.academia.edu/70439702/Defective_transport_of_pyrazolopyrimidine_ribosides_in_insensitive_trypanosoma_cruzi_wild_strains_is_a_parasite_stage_specific_and_reversible_characteristic"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":80191831,"attachmentType":"pdf","workUrl":"https://www.academia.edu/70439702/Defective_transport_of_pyrazolopyrimidine_ribosides_in_insensitive_trypanosoma_cruzi_wild_strains_is_a_parasite_stage_specific_and_reversible_characteristic"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div></div><div data-auto_select="false" data-client_id="331998490334-rsn3chp12mbkiqhl6e7lu2q0mlbu0f1b" data-doc_id="80191831" data-landing_url="https://www.academia.edu/70439702/Defective_transport_of_pyrazolopyrimidine_ribosides_in_insensitive_trypanosoma_cruzi_wild_strains_is_a_parasite_stage_specific_and_reversible_characteristic" data-login_uri="https://www.academia.edu/registrations/google_one_tap" data-moment_callback="onGoogleOneTapEvent" id="g_id_onload"></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":80191831,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":80191831,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_80191831" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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data-author-id="229684187" href="https://independent.academia.edu/RomanoPiras1">Romano Piras</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular and Biochemical Parasitology, 1982</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The effect of inhibitors of macromolecular biosynthesis on the in vitro infectivity and morphology of Trypanosoma cruzi trypomastigotes","attachmentId":96275762,"attachmentType":"pdf","work_url":"https://www.academia.edu/93574974/The_effect_of_inhibitors_of_macromolecular_biosynthesis_on_the_in_vitro_infectivity_and_morphology_of_Trypanosoma_cruzi_trypomastigotes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link 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ds2-5-body-xs">PloS one, 2015</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A Novel Method for Inducing Amastigote-To-Trypomastigote Transformation In Vitro in Trypanosoma cruzi Reveals the Importance of Inositol 1,4,5-Trisphosphate Receptor","attachmentId":44755531,"attachmentType":"pdf","work_url":"https://www.academia.edu/24425057/A_Novel_Method_for_Inducing_Amastigote_To_Trypomastigote_Transformation_In_Vitro_in_Trypanosoma_cruzi_Reveals_the_Importance_of_Inositol_1_4_5_Trisphosphate_Receptor","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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data-author-id="229684187" href="https://independent.academia.edu/RomanoPiras1">Romano Piras</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular and Biochemical Parasitology, 1982</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Changes in morphology and infectivity of cell culture-derived trypomastigotes of Trypanosoma cruzi","attachmentId":96275853,"attachmentType":"pdf","work_url":"https://www.academia.edu/93575097/Changes_in_morphology_and_infectivity_of_cell_culture_derived_trypomastigotes_of_Trypanosoma_cruzi","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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