ICI 174864, a putative delta opioid antagonist, reverses endotoxemic hypotension: pretreatment with dynorphin 1-13, A kappa agonist, blocks this action.

Abstract

The putative delta opioid receptor antagonist ICI 174864 (3 mg/kg, i.v.) significantly reversed endotoxic shock hypotension at a dose which lacked significant pressor actions in normotensive, non-endotoxemic rats. In contrast, dynorphin 1-13, when administered either before (0.1 or 1.0 mg/kg, i.v.) or following (1.0 mg/kg, i.v.) injection of endotoxin, failed to alter the course of ensuing circulatory shock. Additionally, pretreatment with dynorphin 1-13 prevented the subsequent reversal of endotoxemic hypotension by ICI 174864. It is concluded that: 1) delta opioid receptors mediate the endogenous opioid component of endotoxic shock hypotension; and 2) functional interactions occur between ligands for mu, delta, and kappa opioid receptor subtypes, which may predict potential interactions with a common macromolecular opioid receptor complex.

• Authors: J B Long, B A Ruvio, C E Glatt, J W Holaday
• Journal: Neuropeptides (Neuropeptides) Vol. 5 Issue 1-3 Pg. 291-4 (Dec 1984) ISSN: 0143-4179 [Print] Netherlands
• PMID: 6152327 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Peptide Fragments
• Receptors, Opioid
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• Enkephalin, Leucine
• dynorphin (1-13)
• Dynorphins
• N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine

Topics

• Animals
• Blood Pressure (drug effects)
• Dynorphins (pharmacology)
• Enkephalin, Leucine (analogs & derivatives, pharmacology)
• Male
• Peptide Fragments (pharmacology)
• Rats
• Rats, Inbred Strains
• Receptors, Opioid (drug effects, physiology)
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• Shock, Septic (drug therapy)