{"doi":"10.1002/jbmr.5650100511","title":"Thapsigargin stimulates intracellular calcium mobilization and inhibits parathyroid hormone release","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Ca2+ and other divalent cations like Sr2+, Ba2+, and Mg2+ stimulate rapid and sustained increases in intracellular Ca2+ ([Ca2+]i) and 1,4,5-inositol trisphosphate (1,4,5-InsP3) presumably by interacting with recently identified parathyroid cell membrane Ca2+ receptors. We used thapsigargin (THAPS), an inhibitor of the microsomal Ca2+-ATPase, to deplete InsP3-sensitive intracellular Ca2+ stores to determine whether sustained increases in [Ca2+]i due to divalent cations require intact cytosolic Ca2+ pools. In Fura 2-loaded parathyroid cells, THAPS produced a gradual increase in [Ca2+]i which reached a steady-state level by 2–3 minutes. The effect of THAPS (3 × 10−6 M) was substantial with [Ca2+]i, rising from 281 ± 27 nM at 0.5 mM Ca2+ to a peak value of 684 ± 30 nM (p &amp;lt; 0.0001). The addition of Sr2+ to cells at 0.5 mM extracellular Ca2+ induced an immediate 2-to 3-fold increase in [Ca2+]i which stabilized at a [Ca2+]i above baseline for ≥10 minutes. THAPS (3 × 10−6 M) pretreatment for ≥5 minutes blocked this sustained-phase increment in [Ca2+]i due to Sr2+. In the absence of extracellular Ca2+, there was a slight but nonsignificant effect of THAPS on [Ca2+]i. Incubation of cells with THAPS did not change the levels of 3H-inositol phosphates (InsP3, InsP2, and InsP1) or alter Sr2+-induced accumulation of InsP3, InsP2, and InsP1. THAPS substantially reduced parathyroid hormone secretion at 1.0 mM Ca2+ by 20 ± 16, 57 ± 8, 75 ± 10, and 83 ± 9% at 10−7, 3 × 10−7, 10−6, and 3 × 10−6 M THAPS, respectively. We conclude that depletion of intracellular Ca2+ stores by THAPS stimulates Ca2+ mobilization, presumably from extracellular sources, and that this agent and divalent cations such as Sr2+ activate the same pathway for sustained Ca2+ mobilization. The inhibition of secretion by THAPS supports the idea that increases in [Ca2+]i play a suppressive role in the control of hormone release in the parathyroid.</jats:p>","journal":"Journal of Bone and Mineral Research","year":1995,"id":603807,"datarank":0.47032413238937254,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.0,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1548962,"name":"Tsui-Hua Chen","orcid":null,"position":1,"is_corresponding":false},{"id":1548963,"name":"Stacy Pratt","orcid":null,"position":2,"is_corresponding":false},{"id":1548964,"name":"Bruce Lattyak","orcid":null,"position":3,"is_corresponding":false},{"id":1548961,"name":"Dolores Dr. Shoback","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Thapsigargin stimulates intracellular calcium mobilization and inhibits parathyroid hormone release","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Ca2+ and other divalent cations like Sr2+, Ba2+, and Mg2+ stimulate rapid and sustained increases in intracellular Ca2+ ([Ca2+]i) and 1,4,5-inositol trisphosphate (1,4,5-InsP3) presumably by interacting with recently identified parathyroid cell membrane Ca2+ receptors. We used thapsigargin (THAPS), an inhibitor of the microsomal Ca2+-ATPase, to deplete InsP3-sensitive intracellular Ca2+ stores to determine whether sustained increases in [Ca2+]i due to divalent cations require intact cytosolic Ca2+ pools. In Fura 2-loaded parathyroid cells, THAPS produced a gradual increase in [Ca2+]i which reached a steady-state level by 2–3 minutes. The effect of THAPS (3 × 10−6 M) was substantial with [Ca2+]i, rising from 281 ± 27 nM at 0.5 mM Ca2+ to a peak value of 684 ± 30 nM (p &amp;lt; 0.0001). The addition of Sr2+ to cells at 0.5 mM extracellular Ca2+ induced an immediate 2-to 3-fold increase in [Ca2+]i which stabilized at a [Ca2+]i above baseline for ≥10 minutes. THAPS (3 × 10−6 M) pretreatment for ≥5 minutes blocked this sustained-phase increment in [Ca2+]i due to Sr2+. In the absence of extracellular Ca2+, there was a slight but nonsignificant effect of THAPS on [Ca2+]i. Incubation of cells with THAPS did not change the levels of 3H-inositol phosphates (InsP3, InsP2, and InsP1) or alter Sr2+-induced accumulation of InsP3, InsP2, and InsP1. THAPS substantially reduced parathyroid hormone secretion at 1.0 mM Ca2+ by 20 ± 16, 57 ± 8, 75 ± 10, and 83 ± 9% at 10−7, 3 × 10−7, 10−6, and 3 × 10−6 M THAPS, respectively. We conclude that depletion of intracellular Ca2+ stores by THAPS stimulates Ca2+ mobilization, presumably from extracellular sources, and that this agent and divalent cations such as Sr2+ activate the same pathway for sustained Ca2+ mobilization. The inhibition of secretion by THAPS supports the idea that increases in [Ca2+]i play a suppressive role in the control of hormone release in the parathyroid.</jats:p>","is_dataset_classified":null,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"7639110","pmcid":null,"openalex_id":"https://openalex.org/W1988952966","authors":[],"funders":[{"funder_name":"VA Merit Review","grant_id":"R29 DK39594","title":null},{"funder_name":"NIH","grant_id":"DK43400","title":null}],"total_grants":2,"fwci":0.552,"citation_percentile":0.64797766,"influential_citations":0,"citation_trend":[{"year":2014,"count":2},{"year":2018,"count":1}],"oa_status":"closed","license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjbmr.5650100511","host_type":"publisher"},{"url":"https://academic.oup.com/jbmr/article-pdf/10/5/743/56498115/5650100511.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1002/jbmr.5650100511","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/7639110","host_type":"repository"}],"fields_of_study":["Cellular transport and secretion","Ion channel regulation and function","Protein Kinase Regulation and GTPase Signaling"],"mesh_terms":["Calcium-Transporting ATPases","Analysis of Variance","Animals","Calcium","Cations, Divalent","Cattle","Parathyroid Glands","Parathyroid Hormone","Strontium","Terpenes","Inositol 1,4,5-Trisphosphate","Thapsigargin"],"keywords":["Thapsigargin","Extracellular","Divalent","Intracellular","Chemistry","Inositol","Calcium","Fura-2","Biophysics","Inositol trisphosphate","Parathyroid hormone","Cytosol","Endocrinology","Parathyroid chief cell","Inositol phosphate","Internal medicine","Receptor","Biochemistry","Biology","Enzyme","Medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T22:47:03.736714Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}