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Pharmacological characterization of rat VD-hemopressin(α), an α-hemoglobin-derived peptide exhibiting cannabinoid agonist-like effects in mice.

By December 16, 2016 No Comments
Neuropeptides. 2016 Dec 16. pii: S0143-4179(16)30171-8. doi: 10.1016/j.npep.2016.12.006.
[Epub ahead of print]


pm-2-site-207Hemopressin and related peptides have shown to function as the endogenous ligands or the regulator of cannabinoid receptors. Moreover, hemopressin and its truncated peptides were also reported to produce a slight modulatory effect on opioid system. In the present work, based on the amino acid sequence analyses of hemoglobin subunit α, rat VD-hemopressin(α) [(r)VD-Hpα] was predicted as a cannabinoid peptide derived from rat α-hemoglobin. Furthermore, (r)VD-Hpα was synthesized and characterized in a series of in vitro and in vivo assays. Our results demonstrated that (r)VD-Hpα induced neurite outgrowth in Neuro 2A cells via CB1receptor. In the tail-flick assay, (r)VD-Hpα dose-dependently exerted central antinociception through CB1 receptor, but not CB2 and opioid receptors. In mice, supraspinal administration of (r)VD-Hpα produced dose-dependent hypothermia, which was partially reduced by the CB1 receptor antagonist AM251, but not by the antagonists of CB2 and opioid receptors. In addition, (r)VD-Hpα caused hypoactivity after intracerebroventricular injection, and this effect was insensitive to the antagonists of cannabinoid and opioid receptors. Further assessment of the side-effects demonstrated that (r)VD-Hpα evoked the limited effects on gastrointestinal transit at antinociceptive doses, but repeated i.c.v. injection of (r)VD-Hpα induced development of antinociceptive tolerance. Taken together, these data suggest that the predicted peptide (r)VD-Hpα produces antinociception, hypothermia and hypoactivity via different pharmacological mechanisms, at least partially, which may offer an attractive strategy for separating cannabinoid analgesia from hypoactivity. Moreover, it implies that (r)VD-Hpα has therapeutic potential in pain management with limited side-effects.


(r)VD-hemopressin(α); Antinociception; Cannabinoid; Hypoactivity; Hypothermia; Mice; Neurite outgrowth

PMID: 28010996
DOI: 10.1016/j.npep.2016.12.006
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