{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T13:17:09Z","timestamp":1747747029082},"reference-count":0,"publisher":"Canadian Science Publishing","issue":"9","license":[{"start":{"date-parts":[[1994,9,1]],"date-time":"1994-09-01T00:00:00Z","timestamp":778377600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[1994,9,1]]},"abstract":"<jats:p> Barbiturates are known to reduce agonist sensitivity (EC<jats:sub>50<\/jats:sub>) in vascular smooth muscle; we provide evidence that the reduced agonist sensitivity can be correlated with a reduction in agonist affinity for its receptor. The histamine receptor was chosen since this agonist caused a consistent and maximum contraction of the cerebral artery used in this study. Segments of the basilar artery of white New Zealand male rabbits were set up in a small-vessel myograph in physiological salt solution, kept at 37 \u00b0C, pH 7.4, and bubbled with a 95% oxygen and 5% carbon dioxide gas mixture. The equilibrium dissociation constant (K<jats:sub>A<\/jats:sub>) of histamine for its receptor was calculated according to Furchgott's method by making three concentration\u2013response curves to histamine: control, in the presence of phenoxybenzamine (0.02\u2002\u03bcM), and after addition of a barbiturate in concentrations between 0.1 and 1.0\u2002mM. All barbiturates tested, i.e., thiamylal, thiopental, pentobarbital, and phenobarbital, significantly reduced both histamine sensitivity and affinity. There is a significant correlation between histamine sensitivity and receptor affinity for histamine in a series of arterial segments from different animals. The attenuation of both pharmacological properties was consistent with the known rank order of anesthetic potency and with lipophilicity (r\u2002=\u20020.98; p\u2002&lt;\u20020.05). Receptor reserve did not correlate with sensitivity. Thus, most of the change in receptor sensitivity was due to a change in agonist affinity. We suggest that barbiturates alter agonist receptor affinity by causing a perturbation in the membrane lipid environment of the receptor, leading to a conformational change, although alterations in intracellular mechanisms cannot be excluded.Key words: affinity, barbiturates, cerebral arteries, receptors, sensitivity. <\/jats:p>","DOI":"10.1139\/y94-134","type":"journal-article","created":{"date-parts":[[2011,4,24]],"date-time":"2011-04-24T04:59:24Z","timestamp":1303621164000},"page":"963-969","source":"Crossref","is-referenced-by-count":5,"title":["Barbiturate attenuation of agonist affinity in cerebral arteries correlates with anesthetic potency and lipid solubility"],"prefix":"10.1139","volume":"72","author":[{"given":"Peter","family":"Germann","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismail","family":"Laher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Poseno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Bevan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","container-title":["Canadian Journal of Physiology and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nrcresearchpress.com\/doi\/pdf\/10.1139\/y94-134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,5]],"date-time":"2020-01-05T10:19:17Z","timestamp":1578219557000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.nrcresearchpress.com\/doi\/10.1139\/y94-134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,9,1]]},"references-count":0,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1994,9,1]]}},"alternative-id":["10.1139\/y94-134"],"URL":"https:\/\/doi.org\/10.1139\/y94-134","relation":{},"ISSN":["0008-4212","1205-7541"],"issn-type":[{"value":"0008-4212","type":"print"},{"value":"1205-7541","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,9,1]]}}}