{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:34:48Z","timestamp":1740144888128,"version":"3.37.3"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[1990,10,1]],"date-time":"1990-10-01T00:00:00Z","timestamp":654739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AR 39571"],"award-info":[{"award-number":["AR 39571"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1990,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The enzyme carbonic anhydrase has been suggested as a critical participant in osteoclast-mediated bone resorption. In humoral hypercalcemia of malignancy (HHM) intense osteoclastic bone resoprtion is principally responsible for the observed hypercalcemia. We therefore undertook to examine the effect of the carbonic anhydrase inhibitor acetazolamide on the hypercalcemia induced by the H500 Leydig cell tumor in Fisher rats, a well-described model of HHM. Acetazolamide treatment for 10 h at 10 mg\/h resulted in a significant fall in serum calcium in the five drug-treated animals (14.2 \u00b1 0.9 to 11.5 \u00b1 0.1 mg\/dl, p &amp;lt; 0.05). Conversely, the six animals infused with vehicle alone showed a significant rise in serum calcium (12.5 \u00b1 0.5 to 13.8 \u00b1 0.1 mg\/dl, p &amp;lt; 0.05). At the end of the infusion, the acetazolamide-treated animals had a significantly lower mean serum calcium than those receiving vehicle alone (11.5 \u00b1 0.1 versus 13.8 \u00b1 0.1, p &amp;lt; 0.05). There was no significant change in serum phosphorus, urine calcium, urine phosphorus, or nephrogenous cyclic AMP excretion between the two groups. Acetazaolamide and HTS 5-(3-hydroxybenzoyl)-2-thiophenesulfonamide, another carbonic anhydrase inhibitor, both significantly inhibited in vitro bone resorption induced by 5 \u00d7 10\u22129 M 36Tyr(1\u201336)-PTHrP-amide (PTHrP, parathyroid hormone-related protein). Acetazolamide also inhibited the resorption induced by 10\u22128 M (1\u2013141)-PTHrP and 2.5 \u00d7 10\u22129 M (1\u201374)-PTHrP. We conclude that acetazolamide is effective in lowering the serum calcium in animals with humoral hypercalcemia of malignancy. The data are consistent with the hypothesis that the mechanism of action for this effect is direct inhibition of osteoclast-mediated bone resorption.<\/jats:p>","DOI":"10.1002\/jbmr.5650051007","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T18:01:00Z","timestamp":1265220060000},"page":"1037-1041","source":"Crossref","is-referenced-by-count":3,"title":["Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase"],"prefix":"10.1093","volume":"5","author":[{"given":"Gregory M.","family":"Brown","sequence":"first","affiliation":[{"name":"University of Miami School of Medicine, Department of Internal Medicine, 1611 Northwest 12th Avenue, Central Building, Room 600, Miami, FL 33136"},{"name":"Yale University School of Medicine, Department of Internal Medicine, Fitkin 1, P.O. Box 3333, 333 Cedar Street, New Haven, CT 06510"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol A.","family":"Morris","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, Department of Internal Medicine, Fitkin 1, P.O. Box 3333, 333 Cedar Street, New Haven, CT 06510"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Ann","family":"Mitnick","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, Department of Internal Medicine, Fitkin 1, P.O. Box 3333, 333 Cedar Street, New Haven, CT 06510"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl L.","family":"Insogna","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, Department of Internal Medicine, Fitkin 1, P.O. Box 3333, 333 Cedar Street, New Haven, CT 06510"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1990,10,1]]},"reference":[{"key":"2024012712311972500_bib1","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1083\/jcb.101.6.2210","article-title":"Cell-mediated extracellular acidification and bone resorption: Evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border","volume":"101","author":"Baron","year":"1985","journal-title":"J Cell Biol"},{"key":"2024012712311972500_bib2","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1083\/jcb.39.3.676","article-title":"On the mechanisms of bone resorption: The action of parathyroid hormone on the excretion and synthesis of lysosomal enzymes and on the extracellular release of acid by bone cells","volume":"39","author":"Vaes","year":"1969","journal-title":"J Cell 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