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Query: CAS:189388-22-5 (Endomorphin-1)
 112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endomorphin-1, a newly isolated endogenous opioid ligand, has a potential affinity with mu-opioid receptor. We investigated antinociception of intrathecal endomorphin-1 and lidocaine in the rat formalin test and examined the interaction between the two agents using isobolographic analysis. Intrathecal endomorphin-1 caused dose-dependent suppression of the formalin-induced biphasic behavioral response. Intrathecal lidocaine produced dose-dependent inhibition of phase-2 behavioral response. Isobolographic analysis confirmed that combination of intrathecal endomorphin-1 and lidocaine, given at a fixed dose ratio, produced synergistic suppression of phase-2 behavioral response. These data demonstrate that spinal endomorphin-1 synergistically interacts with local anesthetic lidocaine in producing antinociception in the formalin test.
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PMID:Isobolographic analysis of interaction between spinal endomorphin-1, a newly isolated endogenous opioid peptide, and lidocaine in the rat formalin test. 1061 34

Endomorphin-1 and endomorphin-2 were recently postulated to be endogenous mu-opioid receptor agonists. We have investigated the antinociceptive and antihyperalgesic effects of intrathecally administered endomorphins in cumulative doses (0.1-100 microg) on acute and inflammatory pain sensations in awake rats. In the tail-flick test, both peptides caused a dose-dependent short-lasting antinociception, except at the highest dose, which caused motor impairment also. The dose-response curves revealed the development of acute tolerance (tachyphylaxis) to endomorphin. Similarly in the carrageenan-injected paw, the endomorphins (10 microg) exerted transient antinociceptive effects. These are the first data to demonstrate decreased responsivity in models of both acute and inflammatory pain after intrathecal administration of endomorphin-1 and -2 in awake rats.
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PMID:Antinociceptive effects of intrathecal endomorphin-1 and -2 in rats. 1061 71

Recently discovered endomorphin-1 and -2 are the first endogenous agonists selective for the mu-opioid receptor. We examined the antinociceptive effect and enzymatic degradation of endomorphin-1 in the newborn rat spinal cord. Endomorphin-1 inhibited the binding of [3H][D-Ala2, N-Me-Phe4, Gly-ol5] enkephalin (DAMGO) to the membrane fraction of the newborn rat spinal cord as potently as DAMGO and morphine. Endomorphin-1 at 1-1,000 nM reduced the slow ventral root potential, which reflects noxious transmission in the isolated newborn rat spinal cord, concentration-dependently via the mu-opioid receptor. A similar effect was observed with endomorphin-2. The newborn rat spinal cord homogenate degraded endomorphin-1 in a 120-min incubation procedure, while it degraded [Leu5]enkephalin even in a 30-min incubation procedure. The degradation of endomorphin-1 was inhibited by actinonin but not by thiorphan. These results showed that in the newborn rat spinal cord, endomorphins had high affinity for the mu-opioid receptor and exerted mu-opioid-receptor-mediated inhibitory effects on noxious responses. Endomorphin-1 was degraded by peptidases, but slowly compared with [Leu5]enkephalin degradation, and the degrading enzymes were actinonin-sensitive peptidases.
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PMID:Antinociceptive effect and enzymatic degradation of endomorphin-1 in newborn rat spinal cord. 1062 14

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM-1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2) are peptides recently isolated from brain that show the highest affinity and selectivity for the mu (morphine) opiate receptor of all the known endogenous opioids. The endomorphins have potent analgesic and gastrointestinal effects. At the cellular level, they activate G-proteins (35S-GTP gamma-S binding) and inhibit calcium currents. Support for their role as endogenous ligands for the mu-opiate receptor includes their localization by radioimmunoassay and immunocytochemistry in central nervous system regions of high mu receptor density. Intense EM-2 immunoreactivity is present in the terminal regions of primary afferent neurons in the dorsal horn of the spinal cord and in the medulla near high densities of mu receptors. Chemical (capsaicin) and surgical (rhizotomy) disruption of nociceptive primary afferent neurons depletes the immunoreactivity, implicating the primary afferents as the source of EM-2. Thus, EM-2 is well-positioned to serve as an endogenous modulator of pain in its earliest stages of perception. In contrast to EM-2, which is more prevalent in the spinal cord and lower brainstem, EM-1 is more widely and densely distributed throughout the brain than EM-2. The distribution is consistent with a role for the peptides in the modulation of diverse functions, including autonomic, neuroendocrine, and reward functions as well as modulation of responses to pain and stress.
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PMID:Endomorphins: novel endogenous mu-opiate receptor agonists in regions of high mu-opiate receptor density. 1067 42

Endomorphin-1 and endomorphin-2 are recently described peptides with high affinity and specificity for the mu opioid receptor. They are believed to be the endogenous ligands for that receptor. We describe the maturation of the endomorphins in brain and spinal cord using recently characterized antibodies to each. Endomorphin-1-like immunoreactivity was examined in brain, focusing on the periaqueductal gray of the midbrain and the diagonal band of Broca; endomorphin-2-like immunoreactivity is reported for the medulla and spinal cord. In these regions, and in all other regions studied but not described in this paper, the endomorphins were not seen at birth or at 3 days of age. Staining was present in 7-day-old and older animals. At these early ages, the pattern and density of staining are not fully developed, but appear complete by 21 days of age. The results suggest that both endomorphin-1 and endomorphin-2 develop relatively late compared to other opioid peptides.
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PMID:The ontogeny of endomorphin-1- and endomorphin-2-like immunoreactivity in rat brain and spinal cord. 1067 43

Spinal analgesic effects of endomorphin-1 and endomorphin-2 were studied during acute, inflammatory, and neuropathic pain in rats chronically implanted with intrathecal cannulas. Endomorphin-1 and endomorphin-2 (2.5-10 micrograms i.t.), as well as their analogues, increased the tail-flick and the paw pressure latencies. In a model of inflammatory pain, the formalin-induced behavior was attenuated by endomorphins; however, the effect studied was not dose-dependent and was less pronounced in comparison with that evoked by morphine. On the other hand, in rats with a sciatic nerve injury (crush), endomorphins antagonized allodynia in a dose-dependent manner, whereas morphine was found to be ineffective in a similar dose range. Endomorphins also exhibited an antinociceptive potency in rats tolerant to morphine. In conclusion, our results show a powerful analgesic action of endomorphins at the spinal level. The most interesting finding is a strong effect of endomorphins in neuropathic pain, which opens up a possibility of using these compounds in pain therapy.
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PMID:Pain inhibition by endomorphins. 1067 44

The antinociceptive effects of endomorphin-1 and endomorphin-2, endogenous mu-opioid receptor agonists, were examined using the tail-flick test in non-diabetic and diabetic mice. Endomorphin-1, at doses of 1 to 10 microg, i.c.v., and endomorphin-2, at doses of 3 to 30 microg, i.c.v., each dose dependently inhibited the tail-flick response in both non-diabetic and diabetic mice. There was no significant difference between the antinociceptive effects of endomorphin-1 in non-diabetic mice and diabetic mice. The antinociceptive effect of endomorphin-2 was greater in non-diabetic mice than in diabetic mice. In non-diabetic mice, the antinociceptive effects of endomorphin-1 and endomorphin-2 were significantly reduced by beta-funaltrexamine, a mu-opioid receptor antagonist, and naloxonazine, a selective mu(1)-opioid receptor antagonist, but not by naltrindole, a delta-opioid receptor antagonist, or nor-binaltorphimine, a kappa-opioid receptor antagonist. In diabetic mice, the antinociceptive effect of endomorphin-2 was significantly reduced by beta-funaltrexamine and naloxonazine. However, these micro-opioid receptor antagonists had no significant effect on the antinociceptive effect of endomorphin-1 in diabetic mice. The antinociception induced by endomorphin-1 in diabetic mice was significantly reduced by naltrindole and 7-benzylidenenaltrexon, a selective delta(1)-opioid receptor antagonist, administered i.c.v. However, nor-binaltorphimine had no significant effect on the antinociceptive effects of endomorphin-1 and endomorphin-2 in diabetic mice. These results indicate that the antinociceptive effects of endomorphin-1 and endomorphin-2 in non-diabetic mice are mediated through the activation of mu(1)-opioid receptors, whereas in diabetic mice, endomorphin-1 and endomorphin-2 may produce antinociception through different actions at delta(1)- and mu(1)-opioid receptors, respectively.
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PMID:The antinociceptive effects of endomorphin-1 and endomorphin-2 in diabetic mice. 1072 Jun 39

The effects of intracerebroventricular (i.c.v.) administration of endomorphins-1 and -2, endogenous mu-opioid receptor agonists, on the spontaneous alternation performance associated with spatial working memory were investigated in mice. Endomorphin-1 (10 and 17.5 microg) and endomorphin-2 (10 microg) produced a significant decrease in percent alternation without affecting total arm entries. beta-Funaltrexamine (5 microg) almost completely reversed the endomorphin-1 (10 microg)- and endomorphin-2 (10 microg)-induced decrease in percent alternation, although neither naltrindole (4 ng) nor nor-binaltorphimine (4 microg) produced any significant effects on alternation performance. These results suggest that endomorphins impair spatial working memory through the mediation of mu-opioid receptors.
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PMID:Effects of endomorphins-1 and -2, endogenous mu-opioid receptor agonists, on spontaneous alternation performance in mice. 1081 51

Endomorphin-1 is a novel endogenous mu-opioid peptide. In this study, we examined the effects of 2 Hz electroacupuncture in the rat tail flick test and the formalin test (a persistent noxious model). Moreover, we investigated if the electroacupuncture potentiated the effect of intrathecal endomorphin-1. The results demonstrated that electroacupuncture alone produced a significant antinociception in the tail flick test, but not in the formalin test, and that intrathecal endomorphin-1 dose-dependently suppressed the biphasic nociceptive behavior in the formalin test. Electroacupuncture enhanced the antinociceptive effect of intrathecal endomorphin-1 in the formalin test, resulting in a significant leftward shift in the dose-response curves for intrathecal endomorphin-1 antinociception. The enhanced effect was antagonized by intraperitoneal naltrexone. The study suggests that electroacupuncture may potentiate the intrathecal endomorphin-1 antinociception partially mediated by opioid receptors.
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PMID:Electroacupuncture potentiates the antinociceptive effect of intrathecal endomorphin-1 in the rat formalin test. 1084 78

The present study investigated the modulation of N-methyl-D-aspartate (NMDA)-evoked and peripheral cutaneous stimulus-evoked responses of trigeminal neurons by endomorphins, endogenous ligands for the mu-opioid receptor. Effects of endomorphins, administered microiontophoretically, were tested on the responses of nociceptive neurons recorded in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in anesthetized rats. Endomorphin-1 and endomorphin-2 predominantly reduced the NMDA-evoked responses, producing an inhibitory effect of 54.1 +/- 2.96% (mean +/- SE; n = 34, P < 0.001) in 92% (34/37) of neurons and 63.6 +/- 3.61% (n = 32, P < 0.001) in 91% (32/35) of neurons, respectively. The inhibitory effect of endomorphins was modality specific; noxious stimulus-evoked responses were reduced more than nonnoxious stimulus-evoked responses. Naloxone applied at iontophoretic current that blocked the inhibitory effect of [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin, reduced the peak inhibitory effect of endomorphins on the NMDA- and natural stimulus-evoked responses. We suggest that endomorphins by acting at micro-opioid receptor selectively modulate noxious stimulus-evoked responses in the medullary dorsal horn.
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PMID:Endomorphin-1 and endomorphin-2 modulate responses of trigeminal neurons evoked by N-methyl-D-aspartic acid and somatosensory stimuli. 1084 72


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