{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T13:35:08Z","timestamp":1772372108888,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,11,9]],"date-time":"2018-11-09T00:00:00Z","timestamp":1541721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union (FEDER funds)","award":["POCI\/01\/0145\/FEDER\/007265"],"award-info":[{"award-number":["POCI\/01\/0145\/FEDER\/007265"]}]},{"name":"European Union (FEDER funds) and National Funds (FCT\/MEC, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Educa\u00e7\u00e3o e Ci\u00eancia) under the Partnership Agreement PT2020","award":["UID\/QUI\/50006\/2013"],"award-info":[{"award-number":["UID\/QUI\/50006\/2013"]}]},{"name":"European Union (FEDER funds) and National Funds (FCT\/MEC, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Educa\u00e7\u00e3o e Ci\u00eancia) under the Partnership \u201cPrograma Operacional Competitividade e Internacionaliza\u00e7\u00e3o\u201d (COMPETE)","award":["POCI-01-0145-FEDER-029253"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029253"]}]},{"name":"uropean Union (FEDER funds) and National Funds (FCT\/MEC, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Educa\u00e7\u00e3o e Ci\u00eancia) under the the framework of QREN","award":["NORTE-01-0145-FEDER-000024"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>In neutrophils, intracellular Ca2+ levels are regulated by several transporters and pathways, namely SERCA [sarco(endo)plasmic reticulum Ca2+-ATPase], SOCE (store-operated calcium entry), and ROCE (receptor-operated calcium entry). However, the exact mechanisms involved in the communication among these transporters are still unclear. In the present study, thapsigargin, an irreversible inhibitor of SERCA, and ML-9, a broadly used SOCE inhibitor, were applied in human neutrophils to better understand their effects on Ca2+ pathways in these important cells of the immune system. The thapsigargin and ML-9 effects in the intracellular free Ca2+ flux were evaluated in freshly isolated human neutrophils, using a microplate reader for monitoring fluorimetric kinetic readings. The obtained results corroborate the general thapsigargin-induced intracellular pattern of Ca2+ fluctuation, but it was also observed a much more extended effect in time and a clear sustained increase of Ca2+ levels due to its influx by SOCE. Moreover, it was obvious that ML-9 enhanced the thapsigargin-induced emptying of the internal stores. Indeed, ML-9 does not have this effect by itself, which indicates that, in neutrophils, thapsigargin does not act only on the influx by SOCE, but also by other Ca2+ pathways, that, in the future, should be further explored.<\/jats:p>","DOI":"10.3390\/cells7110204","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T03:27:31Z","timestamp":1542079651000},"page":"204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Calcium Pathways in Human Neutrophils\u2014The Extended Effects of Thapsigargin and ML-9"],"prefix":"10.3390","volume":"7","author":[{"given":"Daniela","family":"Ribeiro","sequence":"first","affiliation":[{"name":"LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Marisa","family":"Freitas","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"S\u00edlvia","family":"Rocha","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Jos\u00e9 L. F. C.","family":"Lima","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-3494","authenticated-orcid":false,"given":"F\u00e9lix","family":"Carvalho","sequence":"additional","affiliation":[{"name":"UCIBIO, REQUIMTE, Toxicology Department, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Eduarda","family":"Fernandes","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6407","DOI":"10.1038\/onc.2008.308","article-title":"Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis","volume":"27","author":"Pinton","year":"2008","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1152\/physrev.00020.2014","article-title":"Store-operated calcium channels","volume":"95","author":"Prakriya","year":"2015","journal-title":"Physiol. 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