Chromatin-derived acidic peptides modulate catecholamine release in the hypothalamus.
We have studied the neuromodulatory effects of three synthetic peptides, structurally related to chromatin-derived acidic peptides (ACPs): ACP-1 (Asp-Asp-Ser-Asp-Glu-Glu-Asn), corresponding to the C-terminal fragment of the largest subunit of eukaryotic RNA polymerase II; a more lipophilic derivative, ACP-2 (Ala-Ile-Ser-Pro-Asp-Asp-Ser-Asp-Glu-Glu-Asn); and its phosphorylated form ACP-3 (Ala-Ile-Ser-Pro-Asp-Asp-Ser(P)-Asp-Glu-Glu-Asn). Rat hypothalamic synaptosomes, loaded with [(3)H]norepinephrine or [(3)H]dopamine, were perfused with the above peptides, both basally and during a depolarizing stimulus. We have found: ACP-1 inhibited both dopamine and norepinephrine release; ACP-2 inhibited dopamine release, without affecting norepinephrine release; ACP-3 was almost ineffective, except for a weak dopamine inhibiting effect only at a higher concentration.
Brunetti
L
L
Department of Scienze del Farmaco, G. D'Annunzio University, 66013, Chieti, Italy.
Orlando
G
G
Michelotto
B
B
Recinella
L
L
Vacca
M
M
D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis*; D002843:Chromatin / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000378:metabolism
D002395:Catecholamines; D002843:Chromatin; D010455:Peptides; D004298:Dopamine; D009638:Norepinephrine