{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:51:35Z","timestamp":1767919895843,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,3,23]],"date-time":"2016-03-23T00:00:00Z","timestamp":1458691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) is a gasotransmitter produced from <jats:sc>l<\/jats:sc>\u2010cysteine through the enzymatic action of cystathionine\u2010\u03b3\u2010lyase (CSE) and\/or cystathionine\u2010\u03b2\u2010synthase. <jats:sc>d<\/jats:sc>\u2010Penicillamine is the <jats:sc>d<\/jats:sc> isomer of a dimethylated cysteine and has been used for the treatment of rheumatoid arthritis. As <jats:sc>d<\/jats:sc>\u2010penicillamine is structurally very similar to cysteine, we have investigated whether <jats:sc>d<\/jats:sc>\u2010penicillamine, as a cysteine analogue, has an effect on the H<jats:sub>2<\/jats:sub>S pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We tested the effect of <jats:sc>d<\/jats:sc>\u2010penicillamine (0.01\u20131\u00a0mM) in mouse aortic rings mounted in isolated organ baths and determined whether it could affect H<jats:sub>2<\/jats:sub>S biosynthesis. In particular, we investigated any possible inhibitor or donor behaviour by using recombinant enzyme\u2010based assays and an <jats:italic>in vivo<\/jats:italic> approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:sc>d<\/jats:sc>\u2010Penicillamine, <jats:italic>per se<\/jats:italic>, showed little or no vasodilator effect, and it cannot be metabolized as a substrate in place of <jats:sc>l<\/jats:sc>\u2010cysteine. However, <jats:sc>d<\/jats:sc>\u2010penicillamine significantly reduced <jats:sc>l<\/jats:sc>\u2010cysteine\u2010induced vasodilatation in a concentration\u2010dependent manner through inhibition of H<jats:sub>2<\/jats:sub>S biosynthesis, and this effect occurred at concentrations 10 times lower than those needed to induce the release of H<jats:sub>2<\/jats:sub>S. In particular, <jats:sc>d<\/jats:sc>\u2010penicillamine selectively inhibited CSE in a pyridoxal\u20105\u2032\u2010phospate\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Taken together, our results suggest that <jats:sc>d<\/jats:sc>\u2010penicillamine acts as a selective CSE inhibitor, leading to new perspectives in the design and use of specific pharmacological tools for H<jats:sub>2<\/jats:sub>S research. In addition, the inhibitory effect of <jats:sc>d<\/jats:sc>\u2010penicillamine on CSE could account for its beneficial action in rheumatoid arthritis patients, where H<jats:sub>2<\/jats:sub>S has been shown to have a detrimental effect.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13459","type":"journal-article","created":{"date-parts":[[2016,2,18]],"date-time":"2016-02-18T22:21:25Z","timestamp":1455834085000},"page":"1556-1565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["<scp>d<\/scp>\u2010Penicillamine modulates hydrogen sulfide (<scp>H<sub>2<\/sub>S<\/scp>) pathway through selective inhibition of cystathionine\u2010\u03b3\u2010lyase"],"prefix":"10.1111","volume":"173","author":[{"given":"Vincenzo","family":"Brancaleone","sequence":"first","affiliation":[{"name":"Department of Science University of Basilicata  Potenza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iolanda","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Gargiulo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Vellecco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Asimakopoulou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Patras  Patras Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Citi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Calderone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Pisa  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Gobbetti","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute Queen Mary University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Perretti","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute Queen Mary University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Papapetropoulos","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy University of Athens  Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariarosaria","family":"Bucci","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Cirino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12171"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.217034"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu026"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1016\/S0021-9258(19)85725-3","article-title":"Mechanism\u2010based inactivation of pig heart l\u2010alanine transaminase by l\u2010propargylglycine. 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