Abstract: | α-Melanotropin (α-MSH) retains less than 1% of its original activity after a 60 min incubation with 10% rat brain homogenate. Nle4, D-Phe7]-α-MSH is nonbiodegradable in rat serum (240 min incubation) and still maintains 10% of its original activity in 10% rat brain homogenate (240 min incubation). The related fragment analogue, Ac-Nle4, D-Phe7]-α-MSH4–10-NH2, retains 50% of its activity after a 240 min incubation in rat brain homogenate, whereas Ac-Nle4, D-Phe7]-α-MSH4–11-NH2 is totally resistant to inactivation by rat brain homogenate. Both Nle4, D-Phe7]-fragments are resistant to degradation by rat serum, but Nle4]-α-MSH, Ac-Nle4]-α-MSH4–10-NH2 and Ac-Nle4]-α-MSH4–11-NH2 are rapidly inactivated under both conditions. The cyclic melanotropin,
]-α-MSH, is inactivated in rat brain homogenate as is the shorter Ac-
]-α-MSH4–10-NH2 analogue, but neither cyclic melanotropin is inactivated upon incubation in serum from rats. Ac-
]-α-MSH4–10-NH2 is resistant to inactivation by either rat serum or a brain homogenate. Some of these melanotropin analogues may provide useful probes for the localization and characterization of putative melanotropin receptors in both the central nervous system and peripheral tissues. |