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Antinociceptive effects of central administration of the endogenous cannabinoid receptor type 1 agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(α)], an N-terminally extended hemopressin peptide.
J Pharmacol Exp Ther. 2014 Feb; 348(2):316-23.JP

Abstract

The cannabinoid system has been demonstrated to modulate the acute and chronic pain of multiple origins. Mouse VD-hemopressin(α) [(m)VD-Hpα], an 11-residue α-hemoglobin-derived peptide, was recently reported to function as a selective agonist of the cannabinoid receptor type 1 (CB₁) in vitro. To characterize its behavioral and physiological properties, we investigated the in vivo effects of (m)VD-Hpα in mice. In the mouse tail-flick test, (m)VD-Hpα dose-dependently induced antinociception after supraspinal (EC₅₀ = 6.69 nmol) and spinal (EC₅₀ = 2.88 nmol) administration. The antinociceptive effects of (m)VD-Hpα (intracerebroventricularly and intrathecally) were completely blocked by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamide (AM251; CB₁ antagonist), but not by 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl(4-methoxyphenyl)-methanone (AM630; CB₂ antagonist) or naloxone (opioid antagonist), showing its selectivity to the CB₁ receptor. Furthermore, the central nervous system (CNS) effects of (m)VD-Hpα were evaluated in body temperature, locomotor activity, tolerance development, reward, and food intake assays. At the highly antinociceptive dose (3 × EC₅₀), (m)VD-Hpα markedly exerted hypothermia and hypoactivity after supraspinal administration. Repeated intracerebroventricular injection of (m)VD-Hpα resulted in both development of tolerance to antinociception and conditioned place aversion. In addition, central injection of (m)VD-Hpα dose-dependently stimulated food consumption. These findings demonstrate that this novel cannabinoid peptide agonist induces CB₁-mediated central antinociception with some CNS effects, which further supports a CB₁ agonist character of (m)VD-Hpα. Moreover, the current study will be helpful to understand the in vivo properties of the endogenous peptide agonist of the cannabinoid CB₁ receptor.

Authors+Show Affiliations

Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24307201

Citation

Han, Zheng-lan, et al. "Antinociceptive Effects of Central Administration of the Endogenous Cannabinoid Receptor Type 1 Agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(α)], an N-terminally Extended Hemopressin Peptide." The Journal of Pharmacology and Experimental Therapeutics, vol. 348, no. 2, 2014, pp. 316-23.
Han ZL, Fang Q, Wang ZL, et al. Antinociceptive effects of central administration of the endogenous cannabinoid receptor type 1 agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(α)], an N-terminally extended hemopressin peptide. J Pharmacol Exp Ther. 2014;348(2):316-23.
Han, Z. L., Fang, Q., Wang, Z. L., Li, X. H., Li, N., Chang, X. M., Pan, J. X., Tang, H. Z., & Wang, R. (2014). Antinociceptive effects of central administration of the endogenous cannabinoid receptor type 1 agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(α)], an N-terminally extended hemopressin peptide. The Journal of Pharmacology and Experimental Therapeutics, 348(2), 316-23. https://doi.org/10.1124/jpet.113.209866
Han ZL, et al. Antinociceptive Effects of Central Administration of the Endogenous Cannabinoid Receptor Type 1 Agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(α)], an N-terminally Extended Hemopressin Peptide. J Pharmacol Exp Ther. 2014;348(2):316-23. PubMed PMID: 24307201.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antinociceptive effects of central administration of the endogenous cannabinoid receptor type 1 agonist VDPVNFKLLSH-OH [(m)VD-hemopressin(α)], an N-terminally extended hemopressin peptide. AU - Han,Zheng-lan, AU - Fang,Quan, AU - Wang,Zi-long, AU - Li,Xu-hui, AU - Li,Ning, AU - Chang,Xue-mei, AU - Pan,Jia-xin, AU - Tang,Hong-zhu, AU - Wang,Rui, Y1 - 2013/12/04/ PY - 2013/12/6/entrez PY - 2013/12/7/pubmed PY - 2014/3/4/medline SP - 316 EP - 23 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 348 IS - 2 N2 - The cannabinoid system has been demonstrated to modulate the acute and chronic pain of multiple origins. Mouse VD-hemopressin(α) [(m)VD-Hpα], an 11-residue α-hemoglobin-derived peptide, was recently reported to function as a selective agonist of the cannabinoid receptor type 1 (CB₁) in vitro. To characterize its behavioral and physiological properties, we investigated the in vivo effects of (m)VD-Hpα in mice. In the mouse tail-flick test, (m)VD-Hpα dose-dependently induced antinociception after supraspinal (EC₅₀ = 6.69 nmol) and spinal (EC₅₀ = 2.88 nmol) administration. The antinociceptive effects of (m)VD-Hpα (intracerebroventricularly and intrathecally) were completely blocked by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamide (AM251; CB₁ antagonist), but not by 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl(4-methoxyphenyl)-methanone (AM630; CB₂ antagonist) or naloxone (opioid antagonist), showing its selectivity to the CB₁ receptor. Furthermore, the central nervous system (CNS) effects of (m)VD-Hpα were evaluated in body temperature, locomotor activity, tolerance development, reward, and food intake assays. At the highly antinociceptive dose (3 × EC₅₀), (m)VD-Hpα markedly exerted hypothermia and hypoactivity after supraspinal administration. Repeated intracerebroventricular injection of (m)VD-Hpα resulted in both development of tolerance to antinociception and conditioned place aversion. In addition, central injection of (m)VD-Hpα dose-dependently stimulated food consumption. These findings demonstrate that this novel cannabinoid peptide agonist induces CB₁-mediated central antinociception with some CNS effects, which further supports a CB₁ agonist character of (m)VD-Hpα. Moreover, the current study will be helpful to understand the in vivo properties of the endogenous peptide agonist of the cannabinoid CB₁ receptor. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/24307201/Antinociceptive_effects_of_central_administration_of_the_endogenous_cannabinoid_receptor_type_1_agonist_VDPVNFKLLSH_OH_[_m_VD_hemopressin_α_]_an_N_terminally_extended_hemopressin_peptide_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=24307201 DB - PRIME DP - Unbound Medicine ER -