title: Endomorphins interact with the substance P (SP) aminoterminal SP(1-7) binding in the ventral tegmental area of the rat brain.
abstract: We have recently identified a specific binding site for the tachykinin peptide substance P (SP) fragment SP(1-7) in the rat spinal cord. This site appeared very specific for SP(1-7) as the binding affinity of this compound highly exceeded those of other SP fragments. We also observed that endomorphin-2 (EM-2) exhibited high potency in displacing SP(1-7) from this site. In the present work using a [(3)H]-labeled derivative of the heptapeptide we have identified and characterized [(3)H]-SP(1-7) binding in the rat ventral tegmental area (VTA). Similarly to the [(3)H]-SP(1-7) binding in the spinal cord the affinity of unlabeled SP(1-7) to the specific site in VTA was significantly higher than those of other SP fragments. Further, the tachykinin receptor NK-1, NK-2 and NK-3 ligands showed no or negligible binding to the identified site. However, the mu-opioid peptide (MOP) receptor agonists DAMGO, EM-1 and EM-2 did, and significant difference was observed in the binding affinity between the two endomorphins. As recorded from displacement curves the affinity of EM-2 for the SP(1-7) site was 4-5 times weaker than that for SP(1-7) but about 5 times higher than that of EM-1. The opioid receptor antagonists naloxone and naloxonazine showed weak or negligible binding. It was concluded that the specific site identified for SP(1-7) binding in the rat VTA is distinct from the MOP receptor although it exhibits high affinity for EM-2.
authors.affiliation: Department of Pharmaceutical Biosciences, Uppsala University, SE-751 24 Uppsala, Sweden.
authors.forename: Milad
authors.initials: M
authors.lastname: Botros
authors.forename: Tobias
authors.initials: T
authors.lastname: Johansson
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
authors.forename: Gunnar
authors.initials: G
authors.lastname: Lindeberg
authors.forename: Csaba
authors.initials: C
authors.lastname: Tömböly
authors.forename: Géza
authors.initials: G
authors.lastname: Tóth
authors.forename: Pierre
authors.initials: P
authors.lastname: Le Grevès
authors.forename: Fred
authors.initials: F
authors.lastname: Nyberg
authors.forename: Mathias
authors.initials: M
authors.lastname: Hallberg
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D010446:Peptide Fragments; C105293:endomorphin 1; D013373:Substance P; C105294:endomorphin 2; C036877:substance P (1-7)