{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:27:02Z","timestamp":1781108822394,"version":"3.54.1"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,4,25]]},"abstract":"<jats:p>\n                    Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D\n                    <jats:sub>2<\/jats:sub>\n                    in plasma and could be blocked by pretreatment with aspirin. Two PGD\n                    <jats:sub>2<\/jats:sub>\n                    receptors have been identified: PGD\n                    <jats:sub>2<\/jats:sub>\n                    receptor 1 (DP1, also called DP) and PGD\n                    <jats:sub>2<\/jats:sub>\n                    receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the DP2-specific agonist DK-PGD\n                    <jats:sub>2<\/jats:sub>\n                    (13,14-dihydro-15-keto-PGD\n                    <jats:sub>2<\/jats:sub>\n                    ) did not induce cutaneous vasodilation, and DP2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD\n                    <jats:sub>2<\/jats:sub>\n                    - and NA-induced vasodilation. NA-induced vasodilation was also studied in DP1\n                    <jats:sup>+\/+<\/jats:sup>\n                    , DP1\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    , and DP1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice; although NA-induced vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced vasodilation in male DP\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0601574103","type":"journal-article","created":{"date-parts":[[2006,4,14]],"date-time":"2006-04-14T20:16:00Z","timestamp":1145045760000},"page":"6682-6687","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":238,"title":["Antagonism of the prostaglandin D\n                    <sub>2<\/sub>\n                    receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans"],"prefix":"10.1073","volume":"103","author":[{"given":"Kang","family":"Cheng","sequence":"first","affiliation":[{"name":"Departments of *Cardiovascular Diseases and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuei-Ju","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of *Cardiovascular Diseases and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth K.","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of *Cardiovascular Diseases and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Sturino","sequence":"additional","affiliation":[{"name":"Departments of \u2021Medicinal Chemistry and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Metters","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, Merck Frosst Canada, 16711 Trans Canada Highway, Kirkland, QC, Canada H9H 3L1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Gottesdiener","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Merck Research Laboratories, P.O. 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