Fig. 5. 5-HT is the only biogenic amine that acts as a potent agonist at 5-HT_1Pan and 5-HT_1Pro. (A) Inhibition of forskolin-stimulated cAMP accumulation in response to biogenic amines (10^–3 mol l^–1) in cells induced to express 5-HT_1Pan. Non-induced (NI) cells do not significantly respond to biogenic amines (left). Induced cells show supersensitivity and accumulate significantly higher levels of cAMP in response to forskolin only (grey bars). In induced cells adenylyl cyclase is significantly inhibited in response to 1 mmol l^–1 5-HT but no other biogenic amines (right). Values are means ± s.e.m., N=3, ^#P<0.05 vs non-induced, ^**P<0.001 vs forskolin only. (B) Dose–response curve of 5-HT_1Pan (squares) to 5-HT. The EC₅₀ of 5-HT at 5-HT_1Pan is 8.4 nmol l^–1. Non-induced cells do not show significant changes in forskolin-stimulated cAMP accumulation in response to 5-HT (crosses). Values are means ± s.e.m., N=3. (C) Inhibition of forskolin-stimulated cAMP accumulation in response to amines (10^–3 mol l^–1) in cells induced to express 5-HT_1Pro. Adenylyl cyclase in non-induced cells is activated by dopamine, octopamine and histamine (left). Induced cells accumulate significantly higher levels of cAMP in response to forskolin only (grey bars). In induced cells adenylyl cyclase is significantly inhibited in response to 1 mmol l^–1 5-HT and tyramine but no other biogenic amines (right). As observed in non-induced cells, histamine elicits an increase in cAMP levels in cells expressing 5-HT_1Pro. Values are means ± s.e.m. N=3, ^#P<0.001 vs non-induced, ^**P<0.001 and ^*P<0.05 vs forskolin only. (D) Non-induced (NI) cells show a positive response in cAMP levels at high concentrations of 5-HT (crosses). Owing to this background activity, the dose–response curve of 5-HT_1Pro (black squares) to 5-HT is biphasic. When the activity of non-induced cells in response to 5-HT is subtracted from the response of induced cells (5-HT–NI; grey squares), a sigmoidal dose–response curve is obtained. This curve has an EC50 for 5-HT at 5-HT_1Pro of 31 nmol l^–1. Even at high concentrations tyramine has a minimal effect on 5-HT_1Pro (triangles). Values are means ± s.e.m., N=3.