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Neuropeptides. 2016 Aug;58:15-22. doi: 10.1016/j.npep.2016.02.001. Epub 2016 Feb 3.

Investigation of receptor binding and functional characteristics of hemopressin(1-7).

Author information

1
Laboratory of Chemical Biology, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
2
Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
3
Laboratory of Chemical Biology, Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary. Electronic address: keratti@brc.hu.

Abstract

The orally active, α-hemoglobin derived hemopressin (PVNFKFLSH, Hp(1-9)) and its truncated (PVNFKFL, Hp(1-7) and PVNFKF, Hp(1-6)) and extended ((R)VDPVNFKFLSH, VD-Hp(1-9) and RVD-Hp(1-9)) derivatives have been postulated to be the endogenous peptide ligands of the cannabinoid receptor type 1 (CB1). In an attempt to create a versatile peptidic research tool for the direct study of the CB1 receptor-peptide ligand interactions, Hp(1-7) was radiolabeled and in vitro characterized in rat and CB1 knockout mouse brain membrane homogenates. In saturation and competition radioligand binding studies, [(3)H]Hp(1-7) labeled membrane receptors with high densities and displayed specific binding to a receptor protein, but seemingly not to the cannabinoid type 1, in comparison the results with the prototypic JWH-018, AM251, rimonabant, Hp(1-9) and RVD-Hp(1-9) (pepcan 12) ligands in both rat brain and CB1 knockout mouse brain homogenates. Furthermore, functional [(35)S]GTP γS binding studies revealed that Hp(1-7) and Hp(1-9) only weakly activated G-proteins in both brain membrane homogenates. Based on our findings and the latest literature data, we assume that the Hp(1-7) peptide fragment may be an allosteric ligand or indirect regulator of the endocannabinoid system rather than an endogenous ligand of the CB1 receptor.

KEYWORDS:

Cannabinoid receptor; Hemopressin; Ligand stimulated [(35)S]GTPγS binding assay; Radioligand binding assay; Tritium labeling

PMID:
26895730
DOI:
10.1016/j.npep.2016.02.001
[Indexed for MEDLINE]

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