{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:31:49Z","timestamp":1791045109894,"version":"4.1.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,9,15]]},"abstract":"<jats:p>Dantrolene inhibits and ryanodine stimulates calcium release from skeletal-muscle sarcoplasmic reticulum (SR), the former by an unknown mechanism, and the latter by activating the ryanodine receptor (RyR), the primary Ca2+-release channel of SR. Dantrolene is used to treat malignant hyperthermia (MH), a genetic predisposition to excessive intracellular Ca2+ release upon exposure to volatile anaesthetics. Porcine MH results from a point mutation in the SR RyR that alters the open probability of the channel, and is reflected in altered [3H]ryanodine binding parameters. Specific binding sites for [3H]dantrolene and [3H]ryanodine co-distribute on SR that has been isolated by discontinuous sucrose gradient centrifugation. If the two drug-binding sites are functionally linked, [3H]dantrolene binding might be affected both by pharmacological and by genetic modulators of the functional state of the RyR. Accordingly, we compared the characteristics of [3H]dantrolene binding to porcine malignant-hyperthermia-susceptible and normal-skeletal-muscle SR, and examined the effects of RyR modulators on [3H]dantrolene binding to these membranes. Additionally, the feasibility of separating the SR binding sites for [3H]dantrolene and [3H]ryanodine was investigated. No significant differences in [3H]dantrolene binding characteristics to SR membranes from the two muscle types were detected, and the Bmax ratio for [3H]dantrolene\/[3H]ryanodine was 1.4(\u00b10.1):1 in both muscle types. [3H]Dantrolene binding is unaffected by the RyR modulators caffeine, ryanodine, Ruthenium Red and calmodulin, and neither dantrolene nor azumolene have any effect on [3H]ryanodine binding. Additionally, distinct peaks of [3H]dantrolene and [3H]ryanodine binding are detected in SR membranes fractionated by linear sucrose centrifugation, although no differences in protein patterns are detected by SDS\/PAGE or Western-blot analysis. We suggest that the binding sites for these two drugs are pharmacologically distinct, and may exist on separate molecules.<\/jats:p>","DOI":"10.1042\/bj3260847","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:55:50Z","timestamp":1439243750000},"page":"847-852","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Pharmacological distinction between dantrolene and ryanodine binding sites: evidence from normal and malignant hyperthermia-susceptible porcine skeletal muscle"],"prefix":"10.1042","volume":"326","author":[{"given":"Sanjay S.","family":"PALNITKAR","sequence":"first","affiliation":[{"name":"Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"MICKELSON","sequence":"additional","affiliation":[{"name":"Department of Veterinary PathoBiology, University of Minnesota, St. Paul, MN 55108, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"LOUIS","sequence":"additional","affiliation":[{"name":"Department of Veterinary PathoBiology, University of Minnesota, St. Paul, MN 55108, U.S.A."},{"name":"Department of Biochemistry, University of Minnesota, St. Paul, MN 55108, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"PARNESS","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, U.S.A."},{"name":"Department of Pharmacology and Pediatrics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/326\/3\/847\/625314\/bj3260847.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/326\/3\/847\/625314\/bj3260847.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T01:04:57Z","timestamp":1637715897000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/326\/3\/847\/37668\/Pharmacological-distinction-between-dantrolene-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,9,15]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1997,9,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3260847","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,9,15]]}}}