{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T18:30:32Z","timestamp":1724524232592},"reference-count":70,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":5270,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1990,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although several lines of evidence implicate cyclic AMP in the humoral control of liver growth, its precise role is still not clear. To explore further the role of cyclic AMP in hepatocyte proliferation, we have examined the effects of glucagon and other cyclic AMP\u2010elevating agents on the DNA synthesis in primary cultures of adult rat hepatocytes, with particular focus on the temporal aspects. The cells were cultured in a serum\u2010free, defined medium and treated with epidermal growth factor (EGF), insulin, and dexamethasone. Exposure of the hepatocytes to low concentrations (10 pM\u20101 nM) of glucagon in the early stages of culturing (usually within 6 h from plating) enhanced the initial rate of S phase entry without affecting the lag time from the plating to the onset of DNA synthesis, whereas higher concentrations inhibited it. In contrast, glucagon addition at later stages (24\u201345 h after plating) produced only the inhibition. Thus, if glucagon was added at a time when there was a continuous EGF\/insulin\u2010induced recruitment of cells to S phase, the rate of G<jats:sub>1<\/jats:sub>\u2010S transition was markedly decreased within 1\u20133 h. This inhibitory effect occurred at low glucagon concentrations (ID<jats:sub>50<\/jats:sub> &lt; 1 nM) and was mimicked by cholera toxin, forskolin, isobutyl methylxanthine, and 8\u2010bromo cyclic AMP. The results indicate that cyclic AMP has dual effects on hepatocyte proliferation with a stimulatory modulation early in the prereplicative period (G<jats:sub>o<\/jats:sub> or early G<jats:sub>1<\/jats:sub>), and a marked inhibition exerted immediately before the transition from G<jats:sub>1<\/jats:sub> to S phase.<\/jats:p>","DOI":"10.1002\/jcp.1041440321","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T09:08:43Z","timestamp":1109408923000},"page":"523-530","source":"Crossref","is-referenced-by-count":38,"title":["Dual effects of glucagon and cyclic amp on dna synthesis in cultured rat hepatocytes: Stimulatory regulation in early G<sub>1<\/sub> and inhibition shortly before the s phase entry"],"prefix":"10.1002","volume":"144","author":[{"given":"G. Hege","family":"Thoresen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tor\u2010Erik","family":"Sand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magne","family":"Refsnes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olav F.","family":"Dajani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tormod K.","family":"Guren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivar P.","family":"Gladhaug","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Killi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thoralf","family":"Christoffersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110792"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1986.66.3.499"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041220116"},{"key":"e_1_2_1_5_1","volume-title":"The Biology of Cell Reproduction","author":"Baserga R.","year":"1985"},{"key":"e_1_2_1_6_1","first-page":"193","article-title":"The role of cyclic AMP in cell proliferation: A critical assessment of the evidence","volume":"15","author":"Boynton A. 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