{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T15:07:09Z","timestamp":1794409629577,"version":"4.9.0"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T00:00:00Z","timestamp":1354147200000},"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":[[2012,12]]},"abstract":"\n Background and purpose<\/jats:title>\n \n Pyrazole derivatives have recently been suggested as selective blockers of transient receptor potential cation (\n TRPC<\/jats:styled-content>\n ) channels but their ability to distinguish between the\n TRPC<\/jats:styled-content>\n and\n O<\/jats:styled-content>\n rai pore complexes is ill\u2010defined. This study was designed to characterize a series of pyrazole derivatives in terms of\n TRPC<\/jats:styled-content>\n \/\n O<\/jats:styled-content>\n rai selectivity and to delineate consequences of selective suppression of these pathways for mast cell activation.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental approach<\/jats:title>\n \n Pyrazoles were generated by microwave\u2010assisted synthesis and tested for effects on\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n entry by\n F<\/jats:styled-content>\n ura\u20102 imaging and membrane currents by patch\u2010clamp recording. Experiments were performed in\n HEK<\/jats:styled-content>\n 293 cells overexpressing\n TRPC<\/jats:styled-content>\n 3 and in\n RBL<\/jats:styled-content>\n \u20102\n H<\/jats:styled-content>\n 3 mast cells, which express classical store\u2010operated\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n entry mediated by\n O<\/jats:styled-content>\n rai channels. The consequences of inhibitory effects on\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n signalling in\n RBL<\/jats:styled-content>\n \u20102\n H<\/jats:styled-content>\n 3 cells were investigated at the level of both degranulation and nuclear factor of activated T\u2010cells activation.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n P<\/jats:styled-content>\n yr3, a previously suggested selective inhibitor of\n TRPC<\/jats:styled-content>\n 3, inhibited Orai1\u2010 and\n TRPC<\/jats:styled-content>\n 3\u2010mediated\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n entry and currents as well as mast cell activation with similar potency. By contrast,\n P<\/jats:styled-content>\n yr6 exhibited a 37\u2010fold higher potency to inhibit\n O<\/jats:styled-content>\n rai1\u2010mediated\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n entry as compared with\n TRPC<\/jats:styled-content>\n 3\u2010mediated\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n entry and potently suppressed mast cell activation. The novel pyrazole\n P<\/jats:styled-content>\n yr10 displayed substantial selectivity for\n TRPC<\/jats:styled-content>\n 3\u2010mediated responses (18\u2010fold) and the selective block of\n TRPC<\/jats:styled-content>\n 3 channels by\n P<\/jats:styled-content>\n yr10 barely affected mast cell activation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n The pyrazole derivatives\n P<\/jats:styled-content>\n yr6 and\n P<\/jats:styled-content>\n yr10 are able to distinguish between\n TRPC<\/jats:styled-content>\n and\n O<\/jats:styled-content>\n rai\u2010mediated\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n entry and may serve as useful tools for the analysis of cellular functions of the underlying\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n channels.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/j.1476-5381.2012.02126.x","type":"journal-article","created":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T14:52:40Z","timestamp":1344005560000},"page":"1712-1722","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":191,"title":["Novel pyrazole compounds for pharmacological discrimination between receptor\u2010operated and store\u2010operated\n \n \n Ca\n 2+<\/sup>\n <\/scp>\n <\/scp>\n entry pathways"],"prefix":"10.1111","volume":"167","author":[{"given":"H","family":"Schleifer","sequence":"first","affiliation":[{"name":"Institute of Biophysics Medical University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Doleschal","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences Department of Pharmacology and Toxicology University of Graz Graz 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