Disease relevance of Ici-174864

• Intra-NTS microinjection of 280 fmol of beta-endorphin caused hypotension and bradycardia, and these effects were similarly inhibited by ICI 174864 in SHR and by beta-funaltrexamine in Sprague-Dawley rats [1].
• Neurologic deficits and neuronal injury in rats resulting from nonopioid actions of the delta opioid receptor antagonist ICI 174864 [2].
• Injection into the hilus of dynorphin-A(1-13) after the end of perforant path stimulation, stopped established status epilepticus, while administration of naloxone, naltrindole and ICI-174864 were ineffective [3].
• Whereas hindlimb responses to low doses of ICI 174864 (1.6-6.2 nmol intrathecally) were usually transient, higher doses (6.2-25 nmol intrathecally) produced persistent hindlimb motor dysfunction, altered nociception, priapism, hindlimb edema, bladder infarction and atony and urinary incontinence [2].
• The basal ADP-ribosylation can be abolished by the opioid antagonist ICI 174864, suggesting that unoccupied opioid receptors interact spontaneously with the pertussis toxin substrates Gi/Go in the membrane [4].

High impact information on Ici-174864

• In Sprague-Dawley rats made hypertensive by chronic administration of deoxycorticosterone pivalate and salt, the hypotensive and bradycardic effects of intra-NTS clonidine were inhibited by ICI 174864, but not by beta-funaltrexamine, a pattern similar to that in SHR, but different from that in normotensive Sprague-Dawley rats [1].
• In these membranes, the delta-agonists DSLET and [D-Pen2,D-Pen5]enkephalin still stimulated low-Km GTPase, and these effects were blocked by ICI 174864 (N,N-diallyl-Tyr-AIB-AIB-Phe-Leu-OH; AIB, alpha-aminoisobutyric acid), a delta-selective antagonist [5].
• Chronic treatment with the full delta-agonist [D-Pen(2,5)]-enkephalin reduced the acute ability of [D-Pen(2,5)]-enkephalin to stimulate and the full inverse agonist N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI-174864) to inhibit G protein activation [6].
• Injection into the hilus of the dentate gyrus 10 min prior to stimulation of the kappa-receptor agonist dynorphin-A(1-13), the delta-receptor antagonists ICI-174864 and naltrindole, as well as i.p. injection of naloxone prevented the development of status epilepticus [3].
• This study demonstrates that the selective delta receptor antagonists ICI 174864 and naltrindole (NTI) attenuate alcohol intake in a dose-dependent manner, without altering water intake, in rats selectively bred for alcohol preference [7].

Biological context of Ici-174864

• The loss of receptors was dependent on temperature, with reductions at 37 but not 23 degrees C. The down-regulation was blocked by naloxone and the mu-selective antagonist CTOP (D-Phe-Cys-Tyr-D(-Trp-)Orn-Thr-Pen-Thr-NH2), but not by the delta antagonist ICI 174864 ([N,N-diallyl-Tyr1,Aib2,3]Leu-enkephalin) [8].
• 2. Further experiments show that intra-suprachiasmatic nucleus perfusion of 1 nmol of ICI 174864 or nor-BNI, not beta-FNA, were able to increase the body temperature of hibernating ground squirrels and aroused them from hibernation within 20 hr after the injection [9].

Anatomical context of Ici-174864

• In rats, the spinal subarachnoid injection of the kappa opioid agonist Dynorphin A (Dyn A)(1-13) and the delta opioid receptor antagonist ICI 174864 produced dose-related flaccid paralysis of hindlimbs and tail that were influenced appreciably by injection procedures [10].
• In vitro, ICI 174864 (10(-7) to 10(-4) M) inhibited the twitch in the electrically stimulated mouse vas deferens (ED50 = 90 microM) and guinea pig ileum (ED50 greater than 10(-4) M) [11].
• Neuronal and axonal changes in the lumbosacral spinal cords of rats with persistent and transient neurologic deficits provided direct evidence of the neuropathologic actions of ICI 174864 (3.1 and 6.2 nmol) and ICI 174644 (25 nmol) [2].
• 3. The sympathoinhibitory phase was prevented by injection of the delta-opioid antagonist ICI 174864 (100-300 nmol) or the mu-opioid agonist H-Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (DAMGO) (100-300 pmol) into the fourth cerebral ventricle [12].
• The DPDPE response of striatal mRNA-injected oocytes was antagonized by naloxone as well as the delta-specific antagonist ICI 174864 [13].

Associations of Ici-174864 with other chemical compounds

• I.c.v. injection of 5 micrograms of ICI 174864, a delta-receptor antagonist, potentiated or did not influence clonidine analgesia in SD rats and SHR, respectively [14].
• ICI 174864 was approximately 10 times more potent that TRH at reducing the sleep time [15].

Gene context of Ici-174864

• In contrast to the fiber degeneration, cell loss, and necrosis found in lumbosacral cords of rats persistently paralyzed by other peptides (dynorphin A, somatostatin, and ICI 174864), neuropathological changes were not evident in spinal cords of rats transiently paralyzed by IT AVP [16].
• IL-6 production by macrophages was unaffected except for sporadic incidents of enhanced production in cells exposed to ICI 174864 [17].
• Production of IL-4, however, was significantly suppressed by low concentrations of either TIPP or D-TIPP, and by 10 microM ICI 174864 [17].
• Production of IL-2 by T cells was not consistently affected by exposure to either TIPP or D-TIPP, but was significantly suppressed at 10 microM ICI 174864 [17].
• The incubation of ICI 174864 with carboxypeptidase A generated a peptide, LY281217 [(allyl)2-Tyr-Aib-Aib-Phe-OH], which was a more potent agonist in the mouse vas deferens and guinea pig ileum than ICI 174864 [11].

Analytical, diagnostic and therapeutic context of Ici-174864

• In contrast, the selective delta antagonist, ICI 174864, did not protect the DADLE-induced analgesia against the effect of NEM [18].
• At 10-50 micrograms icv, ICI 174864 had no marked effect on gastrointestinal transit in mice [19].

References