Disease relevance of AIDS-002088

• Other selective mu receptor agonists (morphine sulphate, morphiceptin) caused tachycardia at lower doses (0.64, 6.4 nmol), hypotension and bradypnoea after the highest dose (64 nmol) [1].
• We predicted that Leu-enkephalin would be about 1000-fold more potent than morphiceptin on dorsal root ganglion (DRG) neurons if delta receptors mediated decreases of DRG neuron somatic calcium-dependent action potentials, but that these ligands would be approximately equipotent if mu receptors mediated opiate actions [2].
• The effects of beta-endorphin, morphiceptin, and delta-receptor peptide were reversed with naloxone, although naloxone alone had no effect on lordosis behavior [3].
• Binding of the new morphiceptin analogs to human MCF-7 breast cancer cells and their effect on growth [4].
• Long-term hyperalgesia induced by neonatal beta-endorphin and morphiceptin is blocked by neonatal Tyr-MIF-1 [5].

Psychiatry related information on AIDS-002088

• Morphiceptin in the MPOA had no effect on ex copula genital reflexes, tested in restrained supine males, or on motor activity, tested in a grid box [6].
• Similar injections of morphiceptin into the ventromedial hypothalamus had no effect on any parameter of copulation [6].
• The selective agonist of mu receptors N-MePhe3,-D-Pro4 morphiceptin (PLO 17) produced a stereotyped behavior characterized by stereotyped sniffing and gnawing antagonized by the irreversible antagonist of mu receptors beta-funaltrexamine [7].
• Morphine (0.8-1.75 nmols in 50 nl of saline) and morphiceptin (1.75 nmols) in LC significantly increased the total time spent in slow wave sleep (SWS) and the mean duration of SWS episodes [8].
• The effects on sleep/wakefulness states of morphine, morphiceptin (specific mu agonist), DPDPE (delta agonist) and U-50,488H (kappa agonist) microinjections in the Locus coeruleus area (LC) were studied in cats [8].

High impact information on AIDS-002088

• The synthetic peptide NH2-Tyr-Pro-Phe-Pro-CONH2 (morphiceptin), which is the amide of a fragment of the milk protein beta-casein, has morphinelike activities and is highly specific for morphine (mu) receptors but not for enkephalin (delta) receptors [9].
• Morphiceptin did not activate phospholipase C-mediated phosphatidylinositol hydrolysis but did transiently activate (2- to 3-fold) phospholipase D (PLD), as measured by phosphatidylethanol formation in neuron cultures derived from embryonic day 6 or day 7 cerebral hemispheres [10].
• Both morphiceptin (in a naloxone-reversible manner) and phorbol ester increased phosphorylation of similar cytosolic proteins in intact cells, demonstrating a functional role for the PKC-epsilon activation by opioids [10].
• The mu-opioid peptide morphiceptin stimulated a Ca(2+)-independent protein kinase C (PKC-epsilon) that is expressed both in embryonic day 6 chicken telencephalon and in derived neuronal cultures [10].
• The simultaneous addition of [D-Ala2, D-Leu5]-enkephalin and morphiceptin at concentrations at which 98% of enkephalin (delta) and morphine (mu) receptors are occupied only partially inhibits the binding of [3H]diprenorphine to rat brain membranes [11].

Chemical compound and disease context of AIDS-002088

• The effects of opioid peptides that are highly selective ligands for mu receptors (morphiceptin). delta receptors (delta-receptor peptide), kappa receptors (dynorphin 1-9), and the mu/delta complex (beta-endorphin), were tested on lordosis behavior in ovariectomized rats primed with estrogen and progesterone [3].
• Morphine (10-54 nMol/kg) and DAGO (50 nMol/kg) had no effect on blood pressure, heart rate or respiratory rate; morphiceptin (100-320 nMol/kg) caused tachycardia only at the highest dose [12].
• Morphine and morphiceptin increase the threshold for epinephrine-induced cardiac arrhythmias in the rat through brain mu opioid receptors [13].
• Intracerebroventricular (ICV) infusions of the selective mu receptor agonist morphiceptin produce a dual effect on lordosis behavior in ovariectomized, steroid-primed rats [14].
• Injections of the relative mu agonists Morphine and Morphiceptin the delta agonist D-Ala2, D-Leu5-Enkephalin (DADL) or the putative kappa agonist Dynorphin 1-13 into the HPV caused hypotension and bradypnea; Morphine produced tachycardia while DADL and Dynorphin bradycardia [15].

Biological context of AIDS-002088

• Morphine and the morphinomimetic peptide morphiceptine (Tyr-Pro-Phe-Pro-NH2) displace somatostatin from its binding sites [16].
• Cells pretreated with either the mu-specific opioid agonist morphiceptin (E7CH) or the kappa-specific opioid agonist U69,593 (F-11kappa7) for 24 h showed increased apoptosis in response to staurosporine or wortmannin when compared with non-pretreated cells [17].
• Neither morphiceptin nor U69,593 by themselves had any measurable effect on cell viability or DNA fragmentation, and coaddition of opiates at the same time as staurosporine, wortmannin, or LY294002 did not enhance apoptosis [17].
• Potent morphiceptin analogs: structure activity relationships and morphine-like activities [18].
• The mu and delta selective peptides, morphiceptin and [D-Ala2,D-Leu5]enkephalin, had IC50 values of 87 and 9.2 nM respectively [19].

Anatomical context of AIDS-002088

• Since morphiceptin is a highly specific mu-agonist and can be derived from a milk protein, it is possible that morphiceptin is an exogenous opioid ligand specific for mu-receptors in the brain and gastrointestinal tract [20].
• In contrast, 100 nM VIP significantly increased cAMP production in crypt epithelial cells, which was significantly reduced by both morphiceptin and D-Ser2-Leu-Enk-Thr [21].
• The IC50 values of morphiceptin and its analogs for mu receptor binding were correlated to the ED50 values in the guinea-pig ileum assay, suggesting that the ileum effects were mediated by mu receptor interactions [18].
• A similar correlation between mu receptor binding activity and the ED50 values in the mouse vas deferens assay suggested that morphiceptin and its analogs also acted on mu receptors in this tissue [18].
• Effects of morphiceptin in the medial preoptic area on male sexual behavior [6].

Associations of AIDS-002088 with other chemical compounds

• Two other selective mu agonists, trimu 5 and morphiceptin, inhibited cAMP production in membranes of striatal neurons as well [22].
• Specific [3H]etorphine binding was also demonstrable after preincubation of NIL membranes with DAGO and (Leu5)enkephalin and after preincubation of Ht membranes with morphiceptin and (Leu5)enkephalin; such binding could be displaced by nonradioactive dynorphin A [23].
• First, many DRG neurons responded to dynorphin A but not to morphiceptin or Leu-enkephalin [24].
• In the present study we investigated and compared the in vivo analgesia of centrally administered endomorphin-2 and morphiceptin, and their analogs modified in position 3 [25].
• Microinjections of saline, morphine sulfate, morphiceptin (specific mu agonist), D-pen-2-D-pen-5-enkephalin (delta agonist), and U-50488H (kappa agonist) were given to the freely moving animals (doses 0.8-2.4 x 10(-9) M, in a volume of 0.05 microliters of saline) [26].

Gene context of AIDS-002088

• Furthermore, following intravenous administration of Tyr-Pro-Phe-Pro-NH2, a peptide that is exclusively hydrolyzed by DPP IV, urinary excretion of the peptide in the intact form was many-fold greater in DPP IV-negative rats than in control rats [27].
• Chronic treatment with the low-efficacy mu-selective opioid peptide morphiceptin (10 microM; 3 days), but not with the highly potent mu-agonist DAGO (0.1 microM; 3 days) produced a comparable increase in G-protein abundance [28].
• The intramolecular bridge created by cyclization of morphiceptin prevents dipeptidyl peptidase IV from interacting with these analogues [29].
• [D-1-Nal3]Morphiceptin was the most potent analog of this series with a 26-fold increase in mu-opioid receptor affinity, a 15-fold potency increase in the GPI assay, and a significant potency increase in the hot-plate analgesic test, as compared with morphiceptin [30].
• Interestingly, morphiceptin (a specific mu receptor agonist; 10 micrograms) markedly suppressed LH release, but only sparingly stimulated PRL release [31].

Analytical, diagnostic and therapeutic context of AIDS-002088

• Specific radioimmunoassays have been developed for the measurement of naturally occurring morphiceptin and beta-casomorphin [20].
• Various amounts of the mu-receptor agonists, morphine and morphiceptin, and the delta agonists, D-Ala2-D-Leu5-enkephalin (DADL) and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSLET), were then administered intracerebroventricularly (icv) with continuous EEG monitoring [32].
• The effect of MC was fully present in bilaterally vagotomized rats and in rats under artificial respiration [33].
• Microinjections of morphiceptin and DPDPE failed to alter response thresholds for circling behavior also elicited from electrical stimulation of dorsal PAG [34].
• The intrathecal injection of 1.25, 2.5 and 5 micrograms of [ NMePhe3 ,D-Pro4] morphiceptin (MC), a highly selective mu receptor agonist, in pentobarbital-anesthetized rats resulted in a dose-dependent decrease of mean arterial pressure, reaching a maximal effect 1 h after its administration [33].

References