Structure-activity studies of alpha-melanotropin fragments on cAMP product-ion in striatal slices

In this work, we characterized the active site in the cu-melanotropin hormo ne (alpha-MSH) sequence responsible for the enhancement of cAMP production in incubated striatal slices by using different alpha-MSH fragments. We als o 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 aft er addition of the 6 mu M fragments MSH(1-10), and 0.6 and 6 mu M MSH(5-13) ; however, the values were lower than those induced by 6 mu M alpha-MSH. On the contrary, the addition of MSH(9-13), MSH(7-11), or MSH(6-9), did not a ffect the cAMP content. The presence of 10 mu M SCH23390 blocked the effect of the fragments on cAMP production. We conclude that the biologic activit y of alpha-MSH, as observed through the levels of cAMP, declines when the l ength of its polypeptide chain is shortened, and that the presence of gluta mic acid in the molecule, as well as the core sequence, are of importance f or fragments' activity. (C) 2000 Elsevier Science Inc. All rights reserved.