Table 1

Effects of specific adrenoceptor antagonists and H-89 on α₂and β₂ adrenoceptor agonist-induced hepatocyte DNA synthesis and proliferation in the presence of TGF-α

Treatment	DNA Synthesis (dpm/mg protein/h × 10⁻³)		No. of Nuclei (% of control)
	Culture time (h)		Culture time (h)
	4	21	4	21
Control	2.0 ± 0.2	1.1 ± 0.3	100.3 ± 1.4	99.9 ± 2.7
+prazosin	1.9 ± 0.2	1.1 ± 0.3	100.6 ± 1.5	101.0 ± 1.3
+yohimbine	2.2 ± 0.1	1.3 ± 0.2	100.2 ± 1.7	102.1 ± 3.0
+UK-14304	1.8 ± 0.2	1.3 ± 0.3	100.9 ± 2.1	100.0 ± 2.5
+ metoprolol	2.3 ± 0.2	1.2 ± 0.4	100.4 ± 1.1	100.2 ± 1.7
+ butoxamine	1.6 ± 0.3	1.3 ± 0.7	101.2 ± 1.9	100.7 ± 2.3
+ H-89	1.5 ± 0.3	1.4 ± 0.2	100.3 ± 1.4	102.6 ± 2.5
+ metaproterenol	2.0 ± 0.4	1.2 ± 0.8	101.2 ± 3.3	101.6 ± 2.1
+ 8-br-ocAMP	2.1 ± 0.4	1.7 ± 0.4	101.4 ± 2.1	100.5 ± 1.9
+ glucagon	2.2 ± 0.3	1.2 ± 0.2	102.0 ± 1.6	101.0 ± 1.3
+ forskolin	2.1 ± 0.5	1.1 ± 0.4	100.1 ± 2.0	100.3 ± 2.0
+ dobutamine	1.8 ± 0.4	1.5 ± 0.5	100.3 ± 1.4	100.0 ± 3.1
TGF-α	8.2 ± 0.6^**	8.4 ± 0.6^**	121.1 ± 1.6^**	124.7 ± 1.4^**
+ prazosin	8.3 ± 0.8^**	8.3 ± 0.9^**	120.6 ± 1.3^**	121.0 ± 1.6^**
+ yohimbine	8.6 ± 2.0^**	8.6 ± 1.1^**	120.9 ± 1.1^**	121.0 ± 3.0^**
+ UK-14304	13.6 ± 2.0^**,^†	13.6 ± 1.1^**,^†	133.9 ± 2.1^**,^†	133.0 ± 3.5^**,^†
+ UK-14304 + prazosin	13.1 ± 0.9^**,^†	13.5 ± 1.8^**,^†	134.6 ± 1.3^**,^†	135.0 ± 1.6^**,^†
+ UK-14304 + yohimbine	8.6 ± 2.0^**	8.6 ± 1.1^**	120.9 ± 1.7^**	121.0 ± 2.0^**
+ metoprolol	8.2 ± 1.1^**	8.4 ± 1.0^*	120.4 ± 1.3^**	123.2 ± 1.9^*
+ butoxamine	8.2 ± 1.2^**	8.3 ± 1.0^*	121.2 ± 1.8^**	122.7 ± 2.0^*
+ H-89	8.3 ± 1.0^**	8.4 ± 1.0^*	120.9 ± 1.4^**	123.6 ± 2.9^*
+ metaproterenol	2.6 ± 1.4^††	3.0 ± 1.1^††	101.8 ± 3.1^††	101.4 ± 2.2^††
+ metaproterenol + metoprolol	2.2 ± 0.4^††	3.0 ± 0.3^††	100.8 ± 3.4^††	103.6 ± 2.1^††
+ metaproterenol + butoxamine	8.3 ± 1.0^**	8.3 ± 1.3^*	121.5 ± 1.8^**	124.6 ± 1.5^*
+ metaproterenol + UK-14304	8.0 ± 1.0^**	8.1 ± 1.0^*	120.3 ± 3.1^*	120.0 ± 3.9^*
+ metaproterenol + H-89	8.2 ± 1.4^**	8.6 ± 1.4^**	119.1 ± 2.2^*	120.3 ± 2.7^**
+ 8-br-cAMP	2.2 ± 0.6^††	3.3 ± 1.0^††	102.4 ± 2.3^††	103.5 ± 1.8^††
+ 8-br-cAMP + UK-14304	1.9 ± 0.3^††	2.9 ± 1.3^††	103.2 ± 2.7^††	104.6 ± 2.0^††
+ 8-br-cAMP + H-89	7.7 ± 1.7^*	8.3 ± 1.4^**	119.6 ± 2.6^*	119.9 ± 2.0^**
+ glucagon	2.2 ± 1.0^††	2.0 ± 1.0^††	103.9 ± 1.3^††	104.9 ± 1.3^††
+ forskolin	2.2 ± 0.6^††	2.2 ± 0.4^††	100.1 ± 2.6^††	100.6 ± 2.4^††
+ dobutamine	8.6 ± 1.4^*	8.4 ± 1.1^*	120.3 ± 2.4^**	120.0 ± 3.2^*

Hepatocytes were plated at a density of 3.3 × 10⁴cells/cm². After an attachment period of 3 h, the medium was changed and they were cultured for an additional 4 and 21 h with 1 ng/ml TGF-α alone or with various agents: prazosin, 10⁻⁶ M; yohimbine, 10⁻⁷ M; UK-14304, 10⁻⁵ M; H-89, 10⁻⁷ M; metaproterenol, 10⁻⁷ M; metoprolol, 10⁻⁶ M; butoxamine, 10⁻⁷ M; 8-br-cAMP, 10⁻⁷M; glucagon, 10⁻⁷ M; forskolin, 10⁻⁷ M; dobutamine, 10⁻⁶ M. Each value is expressed as mean ± S.E. from three independent preparations. Values significantly different from those for the control are indicated by ^* P < .05,^** P < .01, Dunnett’s test. Values significantly different from TGF-α alone are indicated by ^† P < .05, ^†† P < .01, Dunnett’s test.