Chromatin-derived acidic peptides modulate catecholamine release in the hypothalamus

We have studied the neuromodulatory effects of three synthetic peptides, st ructurally related to chromatin-derived acidic peptides (ACPs): ACP-1 (Asp- Asp-Ser-Asp-Glu-Glu-Asn), corresponding to the C-terminal fragment of the l argest subunit of eukaryotic RNA polymerase II; a more lipophilic derivativ e, ACP-2 (Ala-Ile-Ser-Pro-Asp-Asp-Ser-Asp-Glu-Glu-Asn); and its phosphoryla ted form ACP-3 (Ala-Ile-Ser-Pro-Asp-Asp-Ser(P)-Asp-Glu-Glu-Asn). Rat hypoth alamic synaptosomes, loaded with [H-3]norepinephrine or [H-3]dopamine, were perfused with the above peptides, both basally and during a depolarizing s timulus. We have found: ACP-I inhibited both dopamine and norepinephrine re lease: ACP-2 inhibited dopamine release, without affecting norepinephrine r elease; ACP-3 was almost ineffective, except for a weak dopamine inhibiting effect only at a higher concentration. (C) 2001 Elsevier Science Inc. All rights reserved.