Stereospecific Binding of the Potent Narcotic Analgesic [
            <sup>3</sup>
            H]Etorphine to Rat-Brain Homogenate

Simon, Eric J.; Hiller, Jacob M.; Edelman, Isidore S.

doi:10.1073/pnas.70.7.1947

Cited by 878 publications

(222 citation statements)

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“…The distinct differences in the response to divalent cations and potencies of the various peptides and alkaloid in displacing the 3H-labeled ligands suggests a difference in the binding sites between f3-endorphin and enkephalin. This dissimilarity in the nature of these peptides' binding also suggests that rapid hydrolysis of enkephalin by brain homogenates (25) might not be the sole explanation for the lack of in vivo analgesic effect displayed by the pentapeptide (11,26). Although [D-Ala2 [Metlenkephalin had potent in vivo analgesic effect (27), the alteration in the secondary structure of the peptide (28) by the D amino acid could not be ignored.…”

Section: Methodsmentioning

confidence: 99%

Properties and localization of beta-endorphin receptor in rat brain.

Law¹,

Loh²,

1979

Proc. Natl. Acad. Sci. U.S.A.

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Thus, by using such a washing procedure with the rapid filtration method, we were able to demonstrate a proteindependent and temperature-dependent high-affinity association of the 13h-[3H]endorphin with the brain membrane (7). Moreover, this high-affinity binding can be demonstrated to be stereospecific (7). The stereoactive isomer levorphanol or (-)naloxone was at least 1000-fold more potent in displacing 3h-[3H]endorphin binding than was the inactive isomer dextrorphan or (+)naloxone, respectively. When the binding of this radioactive ligand was determined at various concentrations and the binding data were analyzed by the method of Scatchard (10), a two-component or single site with negative cooperativity typical of the opiate binding was observed (Fig. 1). The Kd values (with 95% confidence limits) determined from linear regression analysis of the two binding Abbreviation: LPH, lipotropin. 5455The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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Section: Methodsmentioning

confidence: 99%

Properties and localization of beta-endorphin receptor in rat brain.

Law¹,

Loh²,

1979

Proc. Natl. Acad. Sci. U.S.A.

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“…The theoretical underpinning to the action of opioid antagonists is that they interact with opioid receptors and compete with the opiate ligand. 9 In other words, when an opiate molecule enters the bloodstream, it circulates through the body until it comes into contact and binds with an opioid receptor, which [89], [104], [113]. Today we know that there are at least three sub-types of opioid receptor (dubbed µ-, δ-, and κ-opioid receptors), and the genes coding for them have been identified (on chromosomes 6, 1, and 8 in humans, respectively).…”

Section: Opiates and Opioidsmentioning

confidence: 99%

A Theory of Natural Addiction

Smith

Tasnádi

2003

SSRN Journal

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Economic theories of rational addiction aim to describe consumer behavior in the presence of habit-forming goods. We provide a biological foundation for this body of work by formally specifying conditions under which it is optimal to form a habit. We demonstrate the empirical validity of our thesis with an in-depth review and synthesis of the biomedical literature concerning the action of opiates in the mammalian brain and their effects on behavior. Our results lend credence to many of the unconventional behavioral assumptions employed by theories of rational addiction, including adjacent complementarity and the importance of cues, attention, and self-control in determining the behavior of addicts. Our approach suggests, however, that addiction is "harmful" only when the addict fails to implement the optimal solution. We offer evidence for the special case of the opiates that harmful addiction is the manifestation of a mismatch between behavioral algorithms encoded in the human genome and the expanded menu of choices-generated for example, by advances in drug delivery technology-faced by consumers in the modern world.

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“…The discovery and characterization of opioid receptors in vertebrate brain was accomplished with the use of radioligand binding assays (Pert and Snyder, 1973;Simon et al, 1973;Terenius, 1973). Opioid receptors engaged opioid drugs in a stereoselective manner, and were found to be integral membrane proteins located predominantly in neurons.…”

Section: Introductionmentioning

confidence: 99%

Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins

Terskiy

Wannemacher²,

Yadav

et al. 2007

Life Sciences

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Based on the promising opioid pharmacological profile of the peptide, Tyr-Pro-Trp-Gly-NH 2 (Tyr-W-MIF), Zadina et al. (1997) synthesized and screened other Gly 4 -substituted peptides, culminating in the synthesis of Tyr-Pro-Trp-Phe-NH 2 (endomorphin-1), which displayed high affinity and selectivity for the μ opioid receptor. The amidated peptide was then isolated from bovine brain frontal cortex, as was a related peptide, Tyr-Pro-Phe-Phe-NH 2 (endomorphin-2), that displayed similar high affinity and selectivity for the μ opioid receptor. The biosynthesis of the endomorphins in the brain remains obscure, since the putative precursor proteins for the peptides have not been identified. With the completion of the human genome sequencing project, we hypothesized that we should uncover the biological precursors of the peptides using a bioinformatic approach to search the entire human proteome for proteins that contained the endomorphin peptide sequences followed by Gly-Lys/Arg, the consensus sequence for peptide α-amidation and precursor cleavage. Twelve proteins were identified that contained the endomorphin-1 Tyr-Pro-Trp-Phe sequence, however none contained the Tyr-Pro-Trp-Phe-Gly sequence necessary for α-amidation. Twenty-two distinct proteins contained the endomorphin-2 tetrapeptide sequence, and two of those contained the sequence, Tyr-Pro-PhePhe-Gly, however, none contained the requisite peptide-Gly-Lys/Arg sequence. Western blot analysis using an endomorphin-2 antibody detected 4 prominent proteins in mouse brain, necessitating reinterpretation of previous immunocytolocalization studies in the brain. Screening of the current human proteome yielded no evidence for endomorphin precursor proteins based on accepted biochemical criteria.

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Stereospecific Binding of the Potent Narcotic Analgesic [ ³ H]Etorphine to Rat-Brain Homogenate

Abstract: Etorphine, the most potent narcotic analgesic known, was labeled with tritium by catalytic exchange. This drug exhibits stereospecific, saturable binding to rat-brain homogenate. At

Cited by 878 publications

References 8 publications

Properties and localization of beta-endorphin receptor in rat brain.

Properties and localization of beta-endorphin receptor in rat brain.

A Theory of Natural Addiction

Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins

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Stereospecific Binding of the Potent Narcotic Analgesic [ 3 H]Etorphine to Rat-Brain Homogenate

Abstract: Etorphine, the most potent narcotic analgesic known, was labeled with tritium by catalytic exchange. This drug exhibits stereospecific, saturable binding to rat-brain homogenate. At

Cited by 878 publications

References 8 publications

Properties and localization of beta-endorphin receptor in rat brain.

Properties and localization of beta-endorphin receptor in rat brain.

A Theory of Natural Addiction

Search of the human proteome for endomorphin-1 and endomorphin-2 precursor proteins

Contact Info

Product

Resources

About

Stereospecific Binding of the Potent Narcotic Analgesic [ ³ H]Etorphine to Rat-Brain Homogenate