{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T14:13:42Z","timestamp":1775916822696,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R15AT008060"],"award-info":[{"award-number":["R15AT008060"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01DK115478"],"award-info":[{"award-number":["R01DK115478"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Marine cyanobacteria are a rich source of bio-active metabolites that have been utilized as leads for drug discovery and pharmacological tools for basic science research. Here, we describe the re-isolation of a well-known metabolite, barbamide, from Cura\u00e7ao on three different occasions and the characterization of barbamide\u2019s biological interactions with targets of the mammalian nervous system. Barbamide was originally discovered as a molluscicidal agent from a filamentous marine cyanobacterium. In our hands, we found little evidence of toxicity against mammalian cell cultures. However, barbamide showed several affinities when screened for binding affinity for a panel of 45 receptors and transporters known to be involved in nociception and sensory neuron activity. We found high levels of binding affinity for the dopamine transporter, the kappa opioid receptor, and the sigma receptors (sigma-1 and sigma-2 also known as transmembrane protein 97; TMEM97). We tested barbamide in vitro in isolated sensory neurons from female mice to explore its functional impact on calcium flux in these cells. Barbamide by itself had no observable impact on calcium flux. However, barbamide enhanced the effect of the TRPV1 agonist capsaicin and enhanced store-operated calcium entry (SOCE) responses after depletion of intracellular calcium. Overall, these results demonstrate the biological potential of barbamide at sensory neurons with implications for future drug development projects surrounding this molecule.<\/jats:p>","DOI":"10.3390\/md21020110","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T01:40:25Z","timestamp":1675388425000},"page":"110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Barbamide Displays Affinity for Membrane-Bound Receptors and Impacts Store-Operated Calcium Entry in Mouse Sensory Neurons"],"prefix":"10.3390","volume":"21","author":[{"given":"Andrea","family":"Hough","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1115-8802","authenticated-orcid":false,"given":"Connor","family":"Criswell","sequence":"additional","affiliation":[{"name":"Center for Advanced Pain Studies, Department of Neuroscience, University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asef","family":"Faruk","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane E.","family":"Cavanaugh","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-1805","authenticated-orcid":false,"given":"Benedict J.","family":"Kolber","sequence":"additional","affiliation":[{"name":"Center for Advanced Pain Studies, Department of Neuroscience, University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0501-2604","authenticated-orcid":false,"given":"Kevin J.","family":"Tidgewell","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1021\/np960085a","article-title":"Barbamide, a Chlorinated Metabolite with Molluscicidal Activity from the Caribbean Cyanobacterium Lyngbya Majuscula","volume":"59","author":"Orjala","year":"1996","journal-title":"J. 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