Endomorphins fully activate a cloned human mu opioid receptor

Gong, Jianhua; Strong, Judith A.; Zhang, Shengwen; Xia, Yunlong; DeHaven, Robert N.; Daubert, Jeffrey D.; Cassel, Joel; Yu, Guangling; Mansson, Erik; Yu, Lei

doi:10.1016/s0014-5793(98)01362-3

Cited by 50 publications

(21 citation statements)

References 25 publications

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“…5B). This is in agreement with evidence that endomorphin-1 is a partial agonist at the rat -opioid receptor (Hosohata et al, 1998;Sim et al, 1998) (but see Gong et al, 1998). No apparent desensitization of the receptor was observed after 3 hr of treatment of the receptor with 1 M endomorphin-1 (Table 2).…”

Section: Endomorphin-1 Selectively Binds To the Clonedopioid Receptorsupporting

confidence: 90%

Endomorphin-1: Induction of Motor Behavior and Lack of Receptor Desensitization

et al. 2001

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The endomorphins are recently discovered endogenous agonists for the -opioid receptor (Zadina et al., 1997). Endomorphins produce analgesia; however, their role in other brain functions has not been elucidated. We have investigated the behavioral effects of endomorphin-1 in the globus pallidus, a brain region that is rich in -opioid receptors and involved in motor control. Bilateral administration of endomorphin-1 in the globus pallidus of rats induced orofacial dyskinesia. This effect was dose-dependent and at the highest dose tested (18 pmol per side) was sustained during the 60 min of observation, indicating that endomorphin-1 does not induce rapid desensitization of this motor response. In agreement with a lack of desensitization of -opioid receptors, 3 hr of continuous exposure of the cloned receptor to endomorphin-1 did not diminish the subsequent ability of the agonist to inhibit adenylate cyclase activity in cells expressing the cloned -opioid receptor. Confirming the involvement of -opioid receptors, the behavioral effect of endomorphin-1 in the globus pallidus was blocked by the opioid antagonist naloxone and the -selective peptide antagonist Cys 2 -Tyr 3 -Orn 5 -Pen 7 amide (CTOP). Furthermore, the selective receptor agonist [D-Ala 2 -N-Me-Phe 4 -Glycol 5 ]-enkephalin (DAMGO) also stimulated orofacial dyskinesia when infused into the globus pallidus, albeit transiently. Our findings suggest that endogenous agonists may play a role in hyperkinetic movement disorders by inducing sustained activation of pallidal opioid receptors.

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Section: Endomorphin-1 Selectively Binds To the Clonedopioid Receptorsupporting

confidence: 90%

Endomorphin-1: Induction of Motor Behavior and Lack of Receptor Desensitization

et al. 2001

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“…The first saturable transport system across the BBB to be shown for a peptide was for Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH 2 ) (Banks and Kastin 1984). Endomorphin-1 (EM-1) and endomorphin-2 (EM-2), are two endogenous peptides selectively activating mu-opiate receptors (Zadina et al 1997;Goldberg et al 1998;Gong et al 1998;Hosohata et al 1998). The endormorphins are structurally similar to Tyr-MIF-1.…”

Section: Introductionmentioning

confidence: 99%

Endomorphins exit the brain by a saturable efflux system at the basolateral surface of cerebral endothelial cells

Vı́gh

Kastin

Liao

et al. 2004

Experimental Brain Research

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Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) are two highly selective mu-opiate receptor agonists. We recently demonstrated that EM-1 and EM-2 have a saturable transport system from brain-to-blood in vivo. Since the endothelial cells are the main component of the non-fenestrated microvessels of the blood-brain barrier (BBB), we examined whether these endogenous tetrapeptides have a saturable transport system in cultured cerebral endothelial cells. EM-1 and EM-2 binding and transport were studied in a transwell system in which primary mouse endothelial cells were co-cultured with rat glioma cells. We found that binding of both endomorphins was greater on the basolateral than the apical cell surface. Flux of EM-1 and EM-2 occurred predominantly in the basolateral to apical direction, each showing self-inhibition with an excess of the respective endomorphin. Transport was not influenced by the addition of the Pglycoprotein inhibitor, cyclosporin A. Neither the mu-opiate receptor agonist DAMGO nor the delta-opiate receptor agonist DPDPE had any effect on the transport. Thus, the results show that a saturable transport system for EM-1 and EM-2 occurs at the level of endothelial cells of the BBB, and unlike β-endorphin and morphine, P-glycoprotein is not needed for the brain-to-blood transport. Cross-inhibition of the transport of each endomorphin by the other suggests a shared transport system that is different from mu-or delta-opiate receptors. As endormorphins are mainly produced in the CNS, the presence of the efflux system at the BBB could play an important role in pain modulation and neuroendocrine control.

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“…It has been shown that Endos hyperpolarize membrane potential [26], activate inwardly rectified K+ currents [6] and block voltage-dependent Ca 2+ current [4]. However, it is not clear whether Endos reduce synaptic transmission by pre-or postsynaptic mechanism.…”

Section: Endomorphin Inhibition Of Transmitter Release In the Sgmentioning

confidence: 99%

Biomedical Vignette

2000

J Biomed Sci

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Endomorphins fully activate a cloned human mu opioid receptor

Cited by 50 publications

References 25 publications

Endomorphin-1: Induction of Motor Behavior and Lack of Receptor Desensitization

Endomorphin-1: Induction of Motor Behavior and Lack of Receptor Desensitization

Endomorphins exit the brain by a saturable efflux system at the basolateral surface of cerebral endothelial cells

Biomedical Vignette

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