{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:21:01Z","timestamp":1791192061430,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,10,8]],"date-time":"2012-10-08T00:00:00Z","timestamp":1349654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold><jats:italic>N<\/jats:italic>\u2010arachidonoyl 5\u2010HT (NA\u20105HT) has anti\u2010nociceptive effects reported to be mediated by inhibitory actions at the transient receptor potential vanilloid receptor 1 (TRPV1) and fatty acid amide hydrolase (FAAH). Anandamide and<jats:italic>N<\/jats:italic>\u2010arachidonoyl dopamine (NA\u2010DA), endocannabinoids that activate TRPV1 or are metabolized by FAAH, also inhibit T\u2010type calcium channels (<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>). T\u2010type<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>are expressed by many excitable cells, including neurons involved in pain detection and processing. We sought to determine whether NA\u20105HT also modulates T\u2010type<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>Human recombinant T\u2010type<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>(Ca<jats:sub>V<\/jats:sub>3 channels) expressed in HEK 293 cells were examined using standard whole\u2010cell voltage\u2010clamp electrophysiology techniques.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>NA\u20105HT completely inhibited Ca<jats:sub>V<\/jats:sub>3 channels with a rank order of potency (<jats:italic>p<\/jats:italic>EC<jats:sub>50<\/jats:sub>) of Ca<jats:sub>V<\/jats:sub>3.1 (7.4) &gt; Ca<jats:sub>V<\/jats:sub>3.3 (6.8) \u2265 Ca<jats:sub>V<\/jats:sub>3.2 (6.6). The effects of NA\u20105HT were voltage\u2010dependent, and it produced significant hyperpolarizing shifts in Ca<jats:sub>V<\/jats:sub>3 steady\u2010state inactivation relationships. NA\u20105HT selectively affected Ca<jats:sub>V<\/jats:sub>3.3 channel kinetics.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>NA\u20105HT increases the steady\u2010state inactivation of Ca<jats:sub>V<\/jats:sub>3 channels, reducing the number of channels available to open during depolarization. These effects occur at NA\u20105HT concentrations at or below those at which NA\u20105HT affects TRPV1 receptors and FAAH. NA\u20105HT is one of the most potent inhibitors of T\u2010type<jats:italic>I<\/jats:italic><jats:sub>Ca<\/jats:sub>described to date, and it is likely to exert some of its biological effects, including anti\u2010nociception, via inhibition of these channels.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2012.02047.x","type":"journal-article","created":{"date-parts":[[2012,5,24]],"date-time":"2012-05-24T15:40:57Z","timestamp":1337874057000},"page":"1076-1088","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Inhibition of human recombinant T\u2010type calcium channels by<i>N<\/i>\u2010arachidonoyl 5\u2010HT"],"prefix":"10.1111","volume":"167","author":[{"given":"Andrew J","family":"Gilmore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Heblinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kassiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,10,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01649_1.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2919-09.2009"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.2.210"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-1754fje"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8874"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1042\/bj3510817","article-title":"N\u2010acyl\u2010dopamines: novel synthetic CB1 cannabinoid\u2010receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo","volume":"351","author":"Bisogno T","year":"2000","journal-title":"Biochem J"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600515"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-6980(00)00053-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.7033"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610033200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00862.x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2010.02.001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.1.103"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01756-1"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05-4943fje"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/sj.bjp.0707682","article-title":"The role of endocannabinoids in the regulation of gastric emptying: alterations in mice fed a high fat diet","volume":"153","author":"Di Marzo V","year":"2008","journal-title":"Br J Pharmacol"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701272"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.017509"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/1475636031000080216"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.118.5.457"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2011.536532"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(02)75164-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01204.2007"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"e_1_2_8_26_1","unstructured":"HeblinskiM ConnorM(2012).Agonist regulation of 5HT1B receptor signaling. 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