Disease relevance of Endomorphin 1

• The purpose of the present study was to investigate the antinociceptive potency of continuously administered endomorphin-1 on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal test in awake rats [1].
• Endomorphin-1 potentiates HIV-1 expression in human brain cell cultures: implication of an atypical mu-opioid receptor [2].
• At 6 microg, both endomorphin-1 and -2 inhibited lordosis behavior within 30 min [3].
• Naloxone (2 mg/kg, i.v.) completely antagonized the bradycardia and hypotension caused by endomorphin 1 [4].
• Pretreatment of the rats with atropine methylnitrate, atropine sulfate (2 mg/kg, i.v.) or bilateral vagotomy nearly abolished the bradycardia and attenuated the hypotensive effect of endomorphin 1 [4].

Psychiatry related information on Endomorphin 1

• These results suggest that endomorphin-1 improves the disturbance of short-term memory resulting from cholinergic dysfunction through the mediation of mu1-opioid receptors [5].
• In contrast, physostigmine (0.025 and 0.05 mg/kg, i.p.) significantly reversed the endomorphin-1 (10 microg)- and endomorphin-2 (10 microg)-induced disturbance of passive avoidance learning, whereas physostigmine (0.025 and 0.05 mg/kg, i.p.) alone did not influence such learning [6].
• The distribution of EM1 suggests a potential endogenous role for this peptide in major processes modulated by opiates, including affective states and social behavior [7].

High impact information on Endomorphin 1

• OBJECTIVE: To determine whether peripheral administration of the endogenous mu-opioid peptide endomorphin 1 could reduce knee joint pain, using animal models of acute and chronic arthritis [8].
• Furthermore, the analgesic effect of endomorphin 1 is lost during chronic inflammation due to down-regulation of mu-opioid receptor expression in afferent nerve cell bodies [8].
• Endomorphin-1 and dynorphin B inhibited the acetylcholine-evoked currents in alpha9/alpha10-expressing Xenopus oocytes [9].
• CONCLUSION: alpha9/alpha10nAChR is a target for modulation by endomorphin-1 and dynorphin B, efferent cotransmitters in the inner ear [9].
• The endogenous opioid peptides, endomorphin-1 (mu agonist) and dynorphin B (kappa agonist), but not a delta agonist [D-Pen2,D-Pen-5]enkephalin, inhibited the acetylcholine-evoked currents in frog saccular hair cells and rat inner hair cells [9].

Chemical compound and disease context of Endomorphin 1

• Infusions of selective MOR agonists, H-Tyr-d-Ala-Gly-N-Met-Phe-glycinol-enkephalin (DAMGO) or endomorphin-1, into the medial preoptic nucleus attenuated lordosis, and their effects were blocked with the MOR antagonist H-d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) [10].

Biological context of Endomorphin 1

• 3. The IC50 for EM1 and EM2 was 7.7 and 23.1 nM, respectively [11].
• Like nociceptin, microinjection of endomorphin-1 (EM-1), an endogenous ligand for the opioid mu receptor, into the rostral NTS increased blood pressure and heart rate in a dose-dependent manner (0.04, 0.2, and 1 nmol) [12].
• The aim of this study was to examine the role of the endogenous opioid agonist endomorphin 1 (EM-1) in regulating synaptic transmission within the nucleus tractus solitarius (NTS), an integration site for autonomic functions [13].
• Whole-cell patch recordings from substantia gelatinosa neurons of cervical spinal cord slices revealed two conspicuous effects of exogenously applied endomorphin 1 and 2: (i) depression of excitatory postsynaptic potentials evoked by stimulation of dorsal root entry zone, and (ii) hyperpolarization of substantia gelatinosa neurons [14].
• Taken together, the upregulation of MOR and of its endogenous ligands endomorphin-1 and endomorphin-2 in immunocytes suggests an involvement of these opioid peptides in the peripheral control of inflammatory pain [15].

Anatomical context of Endomorphin 1

• Concentration-effect curves of endomorphin-1 and DAMGO in thalamic membranes confirmed that endomorphin-1 produced only 70% of DAMGO-stimulated [35S]GTPgammaS binding [16].
• A series of diastereoisomers of endomorphin-1 (EM1, Tyr(1)-Pro(2)-Trp(3)-Phe(4)-NH(2)) have been synthesized and their potency measured using the guinea pig ileum assay [17].
• Immunohistochemical localization of endomorphin-1 and endomorphin-2 in immune cells and spinal cord in a model of inflammatory pain [15].
• Modulation of synaptic transmission in the rat nucleus of the solitary tract by endomorphin-1 [13].
• Endomorphin-1 and -2 immunoreactive cells in the hypothalamus are labeled by fluoro-gold injections to the ventral tegmental area [18].

Associations of Endomorphin 1 with other chemical compounds

• In the presence of Gbetagamma dimers, the affinities of DAMGO and endomorphin-1 and -2 were higher at hMOR-Galpha(i2) than at hMOR-Galpha(o1), whereas morphine displayed similar affinities at the two chimeras [19].
• The firing rates of both oxytocin and vasopressin cells were reduced by intracerebroventricular endomorphin 1 (5 - 100 pmol); this inhibition was prevented by intravenous naloxone (5 mg kg(-1)) [20].
• A functional assay, based on aequorin-derived luminescence triggered by receptor-mediated changes in intracellular calcium levels, was used to examine relative potency and efficacy of the mu-opioid agonists endomorphin-1, endomorphin-2, morphiceptin, and their position 3-substituted analogs, as well as the delta-agonist deltorphin-II [21].
• We conclude that endomorphin-1 and endomorphin-2 hyperpolarize membranes by opening inwardly-rectifying K(+) channels and attenuate the spontaneous release of l-glutamate from nerve terminals in the substantia gelatinosa, both of which are mediated by mu-opioid receptors, in a manner quantitatively similar to each other [22].
• The expression of mRNA for NOS 2 in J774 macrophages, after 30 min incubation with either lipopolysaccharide or 10(-6) M endomorphin 1 was not upregulated [23].

Gene context of Endomorphin 1

• Immunolabeling for proopiomelanocortin (POMC), the precursor to beta-endorphin, and endomorphin 1 and 2 on sectioned rat forebrain revealed limited labeling consisting of individual varicose fibers [24].
• Similarly, endomorphin-1 suppressed IL-10 and IL-12 productions in response to LPS [25].
• On the contrary, endomorphin-1 inhibited TNF-alpha production by macrophages stimulated with both LPS and PMA, respectively [25].
• METHODS: Different concentrations of beta-endorphin, endomorphin-1 and endomorphin-2 (alone or in combination with the opioid receptor blocker naloxone) as well as different concentrations of cytokines alone (IL-1beta, TNF-alpha) or in combination were applied to in vitro cultured human coronary artery endothelial cells (HCAEC) [26].
• MOR agonists, endomorphin-1 and morphine, induced a rapid (3-min) increase of ERK phosphorylation that was abolished by MOR antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 [27].

Analytical, diagnostic and therapeutic context of Endomorphin 1

• Like enkephalin and nociceptin, perfusion of endomorphin-1 or endomorphin-2 profoundly inhibited spontaneous discharges of 43% and 38% of the medullary neurons, respectively [28].
• Endomorphin-1 potentiated viral expression, in a bell-shaped dose-response manner with maximal enhancement approximately equal to 35% at 10(-10) M, in both mixed glial/neuronal cell and purified microglial cell cultures [2].
• Cardiovascular responses to microinjection of nociceptin and endomorphin-1 into the nucleus tractus solitarii in conscious rats [12].
• The distributions of endomorphin 1 (Tyr-Pro-Trp-Phe-NH2; EM1) and endomorphin 2 (Tyr-Pro-Phe-Phe-NH2; EM2) in the rat central nervous system were determined by immunocytochemistry with two antisera, each demonstrating clear preference for the target antigen [29].
• In the present study, to investigate whether endomorphin 1-immunoreactive and endomorphin 2-immunoreactive neurons in the hypothalamus and nucleus tractus solitarii project reciprocally between these two regions, fluorescent retrograde labeling combined with immunofluorescence histochemical staining for endomorphin 1 and endomorphin 2 was used [30].

References