{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:13Z","timestamp":1760060653594,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15\/01160","RG17-10"],"award-info":[{"award-number":["PI15\/01160","RG17-10"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003946","name":"European Society for Sexual Medicine","doi-asserted-by":"publisher","award":["PI15\/01160","RG17-10"],"award-info":[{"award-number":["PI15\/01160","RG17-10"]}],"id":[{"id":"10.13039\/501100003946","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Benign prostate hyperplasia (BPH) is characterized by prostate enlargement and dynamic alterations contributing to development of lower tract urinary symptoms (LUTS). Prostate hypercontractility has been proposed to contribute to BPH-related LUTS. The aim was to evaluate the effects of inhibiting stromal interaction molecule (STIM)\/Orai calcium entry system on adrenergic and neurogenic contractions in prostate (HP) and bladder neck (HB) strips from BPH patients. Effects of STIM\/Orai inhibition on adrenergic and neurogenic contractions of HP from organ donors (ODs) without BPH were also evaluated. HP and HB strips were obtained from 20 patients with BPH undergoing radical prostatectomy and from six OD at the time of organ collection for transplantation. Tissues were functionally evaluated for isometric tension recording. STIM-1, Orai1, and Orai3 protein expressions were determined in prostate tissues. STIM-1 was also localized by immunofluorescence in prostate sections. Norepinephrine-induced and neurogenic contractions were significantly reduced by STIM\/Orai inhibition with YM-58483 (20 \u00b5M) in HP from BPH patients but not in tissues from ODs. STIM\/Orai inhibition failed to significantly modify contraction of HB from BPH patients. Protein expression of STIM-1 was significantly elevated in HP from BPH patients. Functional contribution of STIM\/Orai system to contractile tone is relevant in prostate when BPH is present, probably related to increased expression of STIM-1. Inhibition of STIM\/Orai could have therapeutic implications for the management of BPH patients by alleviating prostatic hypercontraction.<\/jats:p>","DOI":"10.3390\/ijms26188985","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:56:46Z","timestamp":1758013006000},"page":"8985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Relevance of STIM\/Orai Calcium Entry System Hyperactivation in Human Prostate Contractility in Benign Prostate Hyperplasia"],"prefix":"10.3390","volume":"26","author":[{"given":"Jos\u00e9 M.","family":"La Fuente","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Urologia, Centro Hospitalar e Universit\u00e1rio de Santo Ant\u00f3nio (CHUdSA), 4099-001 Porto, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5390-5677","authenticated-orcid":false,"given":"Mariam","family":"El Assar","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital de Getafe, 28905 Getafe, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n IdiPaz, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Argentina","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Servicio de Histolog\u00eda-Investigaci\u00f3n, Unidad de Investigaci\u00f3n Traslacional en Cardiolog\u00eda\u2013IRYCIS\/UFV, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6551-1333","authenticated-orcid":false,"given":"Leocadio","family":"Rodr\u00edguez-Ma\u00f1as","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n IdiPaz, 28029 Madrid, Spain"},{"name":"Servicio de Geriatr\u00eda, Hospital Universitario de Getafe, 28905 Getafe, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3789-9465","authenticated-orcid":false,"given":"Javier","family":"Angulo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Servicio de Histolog\u00eda-Investigaci\u00f3n, Unidad de Investigaci\u00f3n Traslacional en Cardiolog\u00eda\u2013IRYCIS\/UFV, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.eururo.2013.04.042","article-title":"Future direction in pharmacotherapy for non-neurogenic male lower urinary tract symptoms","volume":"64","author":"Soler","year":"2013","journal-title":"Eur. 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