ICI 174864, a putative delta opioid antagonist, reverses endotoxemic hypotension: pretreatment with dynorphin 1-13, A kappa agonist, blocks this action.
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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004399:Dynorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D012772:Shock, Septic / Q000188:drug therapy*
D010446:Peptide Fragments; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D004743:Enkephalin, Leucine; C026843:dynorphin (1-13); D004399:Dynorphins; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine