Effects of specific beta-1 and beta-2 adrenergic antagonists, UK-14304 and H-89 on metaproterenol- and dibutyryl cAMP-stimulated hepatocyte DNA synthesis and proliferation in the presence of HGF
| Treatment | DNA Synthesis | Number of Nuclei | ||
|---|---|---|---|---|
| Culture time | Culture time | |||
| 4 h | 21 h | 4 h | 21 h | |
| % of control | % of control | |||
| Control | 101.0 ± 19.2 | 100.0 ± 17.8 | 100.0 ± 4.7 | 99.9 ± 3.1 |
| HGF | 1289.4 ± 119.2 | 397.1 ± 43.2 | 132.3 ± 3.2 | 138.3 ± 3.1 |
| +Metaproterenol | 1999.4 ± 164.6* | 617.4 ± 51.7* | 146.8 ± 4.1* | 149.9 ± 3.3 |
| +Propranolol | 1283.9 ± 102.9 | 437.6 ± 42.4 | 129.8 ± 5.1 | 139.3 ± 4.8 |
| +Metaproterenol + propranolol | 1262.0 ± 147.3 | 461.2 ± 33.3 | 131.3 ± 3.4 | 149.2 ± 5.7 |
| +Metoprolol | 1296.8 ± 155.0 | 352.4 ± 34.1 | 134.0 ± 4.0 | 141.3 ± 4.8 |
| +Metaproterenol + metoprolol | 1979.4 ± 168.5* | 577.1 ± 47.1* | 144.1 ± 3.1* | 148.5 ± 3.2 |
| +Butoxamine | 1309.5 ± 135.7 | 383.5 ± 43.2 | 130.6 ± 3.1 | 139.0 ± 4.4 |
| +Metaproterenol + butoxamine | 1219.8 ± 180.7 | 382.1 ± 22.4 | 130.6 ± 3.8 | 139.8 ± 5.0 |
| +Dobutamine | 1255.9 ± 123.1 | 440.8 ± 47.6 | 130.3 ± 4.4 | 140.0 ± 3.4 |
| +UK-14304 | 1305.8 ± 110.9 | 406.9 ± 44.9 | 130.4 ± 4.4 | 139.8 ± 5.2 |
| +Metaproterenol + UK-14304 | 1225.7 ± 119.7 | 479.3 ± 34.3 | 130.8 ± 5.6 | 140.0 ± 4.9 |
| +db-cAMP | 2036.7 ± 167.8* | 684.8 ± 59.0* | 145.9 ± 4.3* | 147.3 ± 4.2 |
| +db-cAMP + UK-14304 | 1894.8 ± 135.7* | 646.6 ± 58.9* | 143.8 ± 3.1* | 144.0 ± 4.8 |
| +H-89 | 1279.7 ± 155.9 | 401.8 ± 43.4 | 132.9 ± 5.0 | 137.7 ± 3.9 |
| +Metaproterenol + H-89 | 1220.1 ± 108.4 | 432.6 ± 49.6 | 137.1 ± 4.2 | 141.3 ± 4.7 |
| +db-cAMP + H-89 | 1233.4 ± 139.4 | 382.7 ± 31.3 | 129.9 ± 5.0 | 139.9 ± 4.0 |
Hepatocytes were plated at a density of 3.3 × 104cells/cm2 and cultured. Specific beta-1 andbeta-2 adrenergic antagonists, UK-14304, H-89, metaproterenol and db-cAMP were added with 5 ng/ml HGF immediately after medium change and cells were cultured for a further 4 h and 21 h. Concentrations were as follows: metaproterenol, 10−7 M; propranolol, 10−5 M; metoprolol, 10−6 M; butoxamine, 10−6 M; dobutamine, 10−6M; UK-14304, 10−6 M; db-cAMP, 10−7 M; H-89, 10−7 M. Values are expressed as mean ± S.E. from three independent preparations. Control values for hepatocyte DNA synthesis and the number of nuclei were 573.7 ± 60.2 dpm/mg protein/h and 3.54 ± 0.15 × 104 nuclei/cm2, respectively. Significant differences from HGF alone are indicated by * P < .05.