Antinociceptive effects of the endogenous cannabinoid peptide agonist VD-hemopressin(β) in mice.

Brain Res Bull. 2018 Feb 6. pii: S0361-9230(17)30762-1. doi: 10.1016/j.brainresbull.2018.02.003.
[Epub ahead of print]

Abstract

PM 2 site 207Cannabinoids (CBs) play important roles in pain modulation. Recently, VD-hemopressin(β) [VD-Hpβ], a 12-residue β-hemoglobin-derived peptide, was reported to activate both CB1 and CB2 receptors in vitro. To further characterize in vivo actions of VD-Hpβ, its antinociceptive activity and site(s) were evaluated in the mouse tail-flick test, and supraspinal antinociception of VD-Hpβ was further assessed in the writhing test. Our results demonstrated that supraspinal, intrathecal, subcutaneous and intraperitoneal administrations of VD-Hpβ produced analgesia in the tail-flick test. When given at the same levels, the CB1 antagonist AM251, rather than the CB2 antagonist AM630 diminished VD-Hpβ-induced antinociception. Furthermore, our results indicated that supraspinal, intrathecal or subcutaneous pretreatment with AM251 significantly inhibited VD-Hpβ-induced systemic antinociception. In the writhing test, supraspinal VD-Hpβ inhibited pain-related behaviors, which was partially prevented by AM251. Notably, supraspinal administration of VD-Hpβ failed to affect motor function at the antinociceptive doses. These findings suggest that VD-Hpβ induces CB1 receptor-mediated antinociception in tail-flick test in various routes of administration, and its systemic antinociception is mediated by both central and peripheral CB1 receptor. In addition, VD-Hpβ produces analgesic activity in the writhing test, which is at least partially mediated by CB1 receptor. Therefore, our present animal models show a CB1 agonistic character of VD-Hpβ, an endogenous cannabinoid peptide.

KEYWORDS:

VD-hemopressin(β); antinociception; cannabinoid; cannabinoid receptor type 1 (CB(1)); mice

PMID: 29425797
DOI: 10.1016/j.brainresbull.2018.02.003
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