The inhibition of human lung fibroblast proliferation and differentiation by Gs-coupled receptors is not predicted by the magnitude of cAMP response

Table 3 Potency and intrinsic activity of all ligands for cAMP accumulation and inhibition of proliferation assays, in HLF

Agonist	cAMP		Proliferation vs serum		Proliferation vs PDGF
Agonist	pEC₅₀	E_max (% max)	pEC₅₀	E_max (% max)	pEC₅₀	E_max (% max)
Treprostinil	6.82 ± 0.06	101 ± 0.58	6.99 ± 0.27	42.5 ± 5.36	7.53 ± 0.12	63.7 ± 6.39
MRE-269	6.75 ± 0.15	52.9 ± 4.36	NC	NC	6.50 ± 0.23	85.7 ± 7.65
Iloprost	7.11 ± 0.34	99.5 ± 7.22	NC	NC	NC	NC
BMY-45778	7.25 ± 0.09	50.0 ± 4.59	ND	ND	ND	ND
Beraprost	6.98 ± 0.08	107 ± 8.99	ND	ND	ND	ND
PGE₂	7.34 ± 0.10	85.5 ± 8.64	7.04 ± 0.18	43.1 ± 6.14	8.60 ± 0.08	71.0 ± 3.86
Misoprostol	6.97 ± 0.06	52.4 ± 6.23	6.74 ± 0.10	34.7 ± 0.71	6.13 ± 0.04	94.1 ± 1.59
Butaprost	5.81 ± 0.16	8.76 ± 3.25	7.19 ± 0.38	29.1 ± 7.29	NC	NC
AGN-205204	6.62 ± 0.12	49.7 ± 3.84	6.91 ± 0.48	51.3 ± 8.89	7.45 ± 0.25	101 ± 3.71
Formoterol	9.38 ± 0.20	103 ± 4.60	9.58 ± 0.29	37.2 ± 2.64	9.08 ± 0.72	70.1 ± 2.96
Indacaterol	8.58 ± 0.20	83.3 ± 4.47	7.96 ± 0.35	47.9 ± 1.58	8.84 ± 0.28	90.3 ± 5.25
Salbutamol	7.36 ± 0.34	68.9 ± 1.40	7.04 ± 0.57	32.4 ± 5.84	7.98 ± 0.17	69.2 ± 5.53
Salmeterol	9.91 ± 0.16	45.8 ± 3.53	9.58 ± 0.14	37.7 ± 7.33	10.5 ± 0.15	89.2 ± 0.27
α-MSH	NC	NC	NC	NC	NC	NC
NECA	5.39 ± 0.13	47.3 ± 3.40	NC	NC	6.94 ± 0.43	37.8 ± 14.7
CGS-21680	NC	NC	NC	NC	NC	NC
BAY60–6583	6.57 ± 0.06	10.2 ± 2.89	5.30 ± 0.16	100 ± 0.01	5.30 ± 0.12	100 ± 0.01
Dopamine	5.39 ± 0.07	41.2 ± 10.0	ND	ND	4.78 ± 0.27	73.5 ± 13.5
Forskolin	NC	NC	5.28 ± 0.13	74.0 ± 6.70	5.98 ± 0.14	90.8 ± 9.12
IBMX	NC	NC	NC	NC	NC	NC
Rolipram	NC	NC	NC	NC	NC	NC

Potency and intrinsic activity values for a range of G_s-coupled receptor agonists, PDE inhibitors, and forskolin in cAMP accumulation and BrdU inhibition assays in HLF. For cAMP accumulation intrinsic activity was calculated as a percentage of the maximal forskolin response. For BrdU inhibition intrinsic activity was calculated as a percentage of maximal proliferation observed with serum or PDGF, as indicated. Data were expressed as means ± SEM for at least 3 independent experiments
NC not calculated due to incomplete curve, ND not determined in this assay

ISSN: 1465-993X