{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:22:08Z","timestamp":1791336128309,"version":"4.3.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,7,21]]},"abstract":"<jats:p>\n                    Cyclic nucleotide phosphodiesterases (PDEs) regulate intracellular levels of cAMP and cGMP by hydrolyzing them to their corresponding 5\u2032 monophosphates. We report here the cloning and characterization of a novel cAMP-specific PDE from mouse testis. This unique phosphodiesterase contains a catalytic domain that overall shares &lt;40% sequence identity to the catalytic domain of all other known PDEs. Based on this limited homology, this new PDE clearly represents a previously unknown PDE gene family designated as PDE8. The cDNA for PDE8 is 3,678 nucleotides in length and is predicted to encode an 823 amino acid enzyme. The cDNA includes a full ORF as it contains an in-frame stop codon before the start methionine. PDE8 is specific for the hydrolysis of cAMP and has a\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>m<\/jats:sub>\n                    of 0.15 \u03bcM. Most common PDE inhibitors are ineffective antagonists of PDE8, including the nonspecific PDE inhibitor 3-isobutyl-1-methylxanthine. Dipyridamole, however, an inhibitor that is generally considered to be relatively specific for the cGMP selective PDEs, does inhibit PDE8 with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 4.5 \u03bcM. Tissue distribution studies of 22 different mouse tissues indicates that PDE8 has highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order.\n                    <jats:italic>In situ<\/jats:italic>\n                    hybridizations in testis, the tissue of highest expression, shows that PDE8 is expressed in the seminiferous epithelium in a stage-specific manner. Highest levels of expression are seen in stages 7\u201312, with little or no expression in stages 1\u20136.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.15.8991","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:50Z","timestamp":1027679750000},"page":"8991-8996","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":243,"title":["Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase"],"prefix":"10.1073","volume":"95","author":[{"given":"S. H.","family":"Soderling","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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