Structure-activity studies of α-melanotropin fragments on cAMP production in striatal slices

In this work, we characterized the active site in the α-melanotropin hormone (α-MSH) sequence responsible for the enhancement of cAMP production in incubated striatal slices by using different α-MSH fragments. We also analyzed the effects of the co-incubation of the SCH23390, a dopaminergic D 1 antagonist, with the MSH fragments, to study the involvement of the D 1 receptor on this induction. A rise was observed in the levels of cAMP after addition of the 6 μM fragments MSH (1–10), and 0.6 and 6 μM MSH (5–13); however, the values were lower than those induced by 6 μM α-MSH. On the contrary, the addition of MSH (9–13), MSH (7–11), or MSH (6–9) did not affect the cAMP content. The presence of 10 μM SCH23390 blocked the effect of the fragments on cAMP production. We conclude that the biologic activity of α-MSH, as observed through the levels of cAMP, declines when the length of its polypeptide chain is shortened, and that the presence of glutamic acid in the molecule, as well as the core sequence, are of importance for fragments′ activity.