Antinociceptive action of hemopressin in experimental hyperalgesia

Dale, Camila S.; Pagano, Rosana L.; Rioli, Vanessa; Hyslop, Stephen; Giorgi, Renata; Ferro, Emer S.

doi:10.1016/j.peptides.2004.10.026

Cited by 63 publications

(58 citation statements)

References 33 publications

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“…4A). In this pain model (paw-pressure test), hemopressin on its own has no antihyperalgesic action (15). We also found that hemopressin administered intrathecally (Fig.…”

Section: Resultssupporting

confidence: 52%

“…Because this panel contains hemopressin (PVNFKFLSH) that was found to have nonopioid receptor mediated antinociceptive effects (15), we decided to screen CB 1 cannabinoid receptors. For screening the peptides, we used a recently described ELISA with anti-CB 1 receptor antibodies; these antibodies are sensitive to activity-mediated conformational changes in the receptors and thus are able to differentially recognize different activity states of the receptors (16).…”

Section: Resultsmentioning

confidence: 99%

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Hemopressin is an inverse agonist of CB ₁ cannabinoid receptors

Heimann

Gomes

Dale

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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222

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To date, the endogenous ligands described for cannabinoid receptors have been derived from membrane lipids. To identify a peptide ligand for CB 1 cannabinoid receptors, we used the recently described conformation-state sensitive antibodies and screened a panel of endogenous peptides from rodent brain or adipose tissue. This led to the identification of hemopressin (PVNFKFLSH) as a peptide ligand that selectively binds CB 1 cannabinoid receptors. We find that hemopressin is a CB 1 receptor-selective antagonist, because it is able to efficiently block signaling by CB 1 receptors but not by other members of family A G protein-coupled receptors (including the closely related CB2 receptors). Hemopressin also behaves as an inverse agonist of CB 1 receptors, because it is able to block the constitutive activity of these receptors to the same extent as its well characterized antagonist, rimonabant. Finally, we examine the activity of hemopressin in vivo using different models of pain and find that it exhibits antinociceptive effects when administered by either intrathecal, intraplantar, or oral routes, underscoring hemopressin's therapeutic potential. These results represent a demonstration of a peptide ligand for CB 1 cannabinoid receptors that also exhibits analgesic properties. These findings are likely to have a profound impact on the development of novel therapeutics targeting CB 1 receptors.

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“…4A). In this pain model (paw-pressure test), hemopressin on its own has no antihyperalgesic action (15). We also found that hemopressin administered intrathecally (Fig.…”

Section: Resultssupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Hemopressin is an inverse agonist of CB ₁ cannabinoid receptors

Heimann

Gomes

Dale

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

222

240

View full text Add to dashboard Cite

show abstract

“…These effects were not inhibited by naloxone, indicating that opioid receptors are not involved and that the effect of hemopressin on pain sensitivity is via an action on the (Dale et al 2004).…”

Section: Biological Functions Of Hemopressinmentioning

confidence: 89%

“…In a recent work by Dale et al (2004), hemopressin (10 µg/paw) reverted the hyperalgesia induced by either carrageenin or bradykinin when injected concomitantly or 2.5 h after injection of the phlogistic agents. These effects were not inhibited by naloxone, indicating that opioid receptors are not involved and that the effect of hemopressin on pain sensitivity is via an action on the (Dale et al 2004).…”

Section: Biological Functions Of Hemopressinmentioning

confidence: 90%

“…Two fragments of hemopressin (PVNFKF and PVNFKFL) were as effective as hemopressin in exerting an antihyperalgesic action, thus indicating that intact hemopressin was not essential for the expression of full antinociceptive activity; however, shorter fragments (PVNFK and PVNF) were inactive (Dale et al 2004). Curiously, the order of activity of these fragments on blood pressure is the exact opposite of that seen for analgesia.…”

Section: Biological Functions Of Hemopressinmentioning

confidence: 99%

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