{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:44:06Z","timestamp":1787013846610,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071637"],"award-info":[{"award-number":["82071637"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2008085QH420"],"award-info":[{"award-number":["2008085QH420"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recently, dapoxetine has been widely accepted to treat premature ejaculation by fast\u2010inhibiting 5\u2010hydroxytryptamine reuptake. However, dapoxetine is not suitable for all premature ejaculation patients in clinical treatment. We need to investigate and reveal the mechanism deeply to solve this problem.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate and reveal the function of dopamine D4 receptor in dapoxetine medicated premature ejaculation treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A rat model was used to screen rapid ejaculators. The molecular mechanisms of histone serotonylation\u2010mediated regulation of dopamine D4 receptor were demonstrated by chromatin immunoprecipitation, DNA pull\u2010down, mass spectrometry analysis, and coimmunoprecipitation experiments. The biological function of dopamine D4 receptor was investigated through in vivo experiments by intrathecal injection of shDRD4 to knockdown dopamine D4 receptor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, we found that dapoxetine increased expression of 5\u2010hydroxytryptamine and dopamine D4 receptor. We demonstrated that dapoxetine increased levels of 5\u2010hydroxytryptamine, which promoted histone serotonylation (H3K4me3Q5ser) and transcription factor myeloid zinc\u2010finger 1 complex binding on the dopamine D4 receptor promoter, upregulated the expression of dopamine D4 receptor and thus delayed ejaculation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In this study, we demonstrated that dapoxetine increased the levels of 5\u2010hydroxytryptamine, which promoted histone serotonylation and myeloid zinc\u2010finger 1 complex binding to the dopamine D4 receptor promoter and upregulated the expression of dopamine D4 receptor, thus delaying ejaculation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>It is a novel mechanism that dapoxetine take effect of premature ejaculation treatment through upregulating the dopamine D4 receptor, which indicated that upregulated dopamine D4 receptor would enhance the dapoxetine effect in premature ejaculation treatment. This may lead to the development of novel therapeutic interventions for premature ejaculation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.13390","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T22:24:12Z","timestamp":1675722252000},"page":"1175-1187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Vital function of DRD4 in dapoxetine medicated premature ejaculation treatment"],"prefix":"10.1111","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0973-7845","authenticated-orcid":false,"given":"Pan","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Anhui Medical 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