Specificity of opioids towards the μ-, δ- and ϵ-opiate receptors

Wüster, Michael; Schulz, Rüdiger; Herz, A.

doi:10.1016/0304-3940(79)96112-3

Cited by 199 publications

(42 citation statements)

References 6 publications

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“…The sensitivity against opioid peptides of three kinds of isolated preparations employed in the present study, therefore, was confirmed to be essentially the same as that used in the previous studies (1)(2)(3)(4)(5)(6) significantly alter the inhibitory potency of ;3-endorphin in both guinea-pig ileum and rat vas deferens, but significantly augmented the potency of (3-endorphin in mouse vas deferens ( Table 4). The observation that the potency of enkephalins relative to that of 3 endorphin in rat vas deferens was significantly lower than that in the other two preparations in the absence of peptidase inhibitors, therefore, was shown to be partly caused by the presence of the higher activity of enkephalin-hydrolyzing peptidases in rat vas deferens than in the other two preparations.…”

Section: Resultssupporting

confidence: 85%

“…It is well-known that [Met5]-enkephalin is more potent than [Leu5]-enkephalin in guinea-pig ileum, while the latter is more potent than the former in mouse vas deferens (1,2). Additionally, it is reported that ,3 endorphin has either approximately the same potency as, or slightly higher potency than, [Met5]-enkephalin in guinea-pig ileum, while the latter is more potent than the former in mouse vas deferens (3,4).…”

Section: Abstract-previousmentioning

confidence: 99%

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The Relative Potency of Enkephalins and β-Endorphin in Guinea-Pig Ileum, Mouse Vas Deferens and Rat Vas Deferens after the Administration of Peptidase Inhibitors

Kuno

Aoki

Kajiwara

et al. 1986

Japanese Journal of Pharmacology

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Abstract-Previousstudies have shown that three distinct enzymes, amastatin sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A, and phos phoramidon-sensitive endopeptidase-24.11, played a critical role in the inactivation of enkephalins in isolated preparations.In the present study, therefore, the rank order of the potency of three endogenous opioid peptides,and i3-endorphin, in three isolated preparations, guinea-pig ileum, mouse vas deferens, and rat vas deferens, was estimated in the presence of the mixture of three peptidase inhibitors, amastatin, captopril, and phosphoramidon.[Met5]-Enkephalin was approximately three-fold more potent than [Leu5] enkephalin and four-fold more potent than ,3-endorphin in guinea-pig ileum in which three opioid peptides were indicated to act on mu-receptors.Additionally, [Met5]-enkephalin was slightly but significantly more potent than [Leu5] enkephalin and approximately twenty-fold more potent than ,3-endorphin at delta receptor sites in mouse vas deferens.Moreover, [Met5]-enkephalin was ap proximately three-fold more potent than [Leu5]-enkephalin, but sixty-fold less potent than ,3-endorphin in rat vas deferens in which the opioid-receptor type interacting with enkephalins could not be determined.In conclusion, the well known rank order of the potency of three endogenous opioid peptides was shown to be altered in both guinea-pig ileum and mouse vas deferens but not in rat vas deferens by the pretreatment of the preparations with the mixture of three peptidase inhibitors.

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Section: Resultssupporting

confidence: 85%

Section: Abstract-previousmentioning

confidence: 99%

The Relative Potency of Enkephalins and β-Endorphin in Guinea-Pig Ileum, Mouse Vas Deferens and Rat Vas Deferens after the Administration of Peptidase Inhibitors

Kuno

Aoki

Kajiwara

et al. 1986

Japanese Journal of Pharmacology

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“…Our results, taken together with the studies of Goldstein and his colleague on dynorphin binding sites (Chavkin & Goldstein 1981), suggested that opiate receptors interact with complementary opioid peptides, β-endorphin acting preferentially at a 'β-endorphin receptor' (possibly the ε receptor present in rat vas deferens (Hammonds et al 1984) or the μ receptor in guinea pig ileum (Paterson et al 1983)), dynorphin at a 'dynorphin receptor' (the κ receptor (Chavkin & Goldstein 1981)) and enkephalin at an 'enkephalin receptor' (the δ receptor present in mouse vas deferens (Wuster et al 1979)). The hypothesis proposed that each functional opioid peptide is targetted at a corresponding receptor, ensuring that opiate activity is focused at the site where the appropriate receptor is situated.…”

Section: T19 Thematic Reviewmentioning

confidence: 99%

60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective

Smyth

2016

Journal of Molecular Endocrinology

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Many important fields of research had a humble origin. In the distant past, A J P Martin's discovery that amino acids could be separated by paper chromatography and Moore and Stein's use of columns for quantitative amino acid analysis provided the first steps towards the determination of structure in complex biologically active molecules. They opened the door to reveal the essential relationship that exists between structure and function. In molecular endocrinology, for example, striking advances have been made by chemists with their expertise in the identification of structure working with biologists who contributed valuable knowledge and experience. Advantage was gained from the convergence of different background, and it is notable that the whole is greater than the sum. In the determination of structure, it may be recalled that four of the world's great pioneers (Archibald Martin, Rodney Porter, Fred Sanger and Vincent du Vigneaud) were acknowledged for their fundamental contributions when individually they were awarded the Nobel Prize. They foresaw that the identification of structure would prove of outstanding importance in the future. Indeed, study of the structures of β-endorphin and enkephalin and the different forms of opiate activity they engender has led to a transformation in our understanding of chemical transmission in the brain.

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“…A recent double-blind randomised study comparing the respiratory depression induced by equipotent doses of morphine and M6G in normal volunteers (Thompson et al, 1990) (Gilbert & Martin, 1976;Lord et al, 1977;Wuster et al, 1979;Wolozin et al, 1981;Pasternak et al, 1980. Gouarderes et al, 1981Rothman & Westfall, 1982), but there remains controversy over the existence and the functional and structural relationships of the various opioid receptor subtypes, particularly of the mu and delta receptor.…”

mentioning

confidence: 99%

Explanation at the opioid receptor level for differing toxicity of morphine and morphine 6-glucuronide

Hucks

Thompson²,

McLoughlin³

et al. 1992

Br J Cancer

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Summary The radiolabelled opioid receptor binding affinities of morphine and its active metabolite morphine 6-glucuronide at the total mu, mu 1, mu 2 and delta receptors were determined. Morphine 6-glucuronide was found to have a 4-fold lower affinity for the mu 2 receptor (IC50 17 nm and 82 nm for morphine and morphine 6-glucuronide respectively, P = 0.01), the receptor postulated to be responsible for mediating the respiratory depression and gastrointestinal effects after morphine. This provides a possible explanation for the reduced respiratory depression and vomiting seen following morphine 6-glucuronide in man. A similar reduction in affinity of morphine 6-glucuronide was seen at the total mu receptor whilst there was no significant difference seen at the mu or delta receptor. Hence the increased analgesic potency of morphine 6-glucuronide over morphine remains unexplained.Morphine is one of the commonest drugs prescribed by cancer physicians and is an effective potent analgesic. However one or more of the side effects of constipation, nausea and vomiting, and sedation are encountered frequently (Jaffe & Martin, 1991). Respiratory depression is a less common problem but is the most potentially dangerous toxicity. An analgesic with equivalent potency but lower toxicity would therefore be of particular use.The major metabolic products of morphine are morphine 3-glucuronide (M3G) and morphine 6-glucuronide (M6G). Although M3G is devoid of analgesic activity, M6G is now thought to play a major role in mediating the analgesic effect of morphine (Osborne et al., 1986;Hanks et al., 1987;Hoskin & Hanks, 1990 Pasternak, 1981). This model suggests there is a common receptor labelled by either a prototypic delta agonist such as DADLE (D-Ala2, D-Leu5-enkephalin) or with a mu agonist such as morphine which has high affinity for morphine. This they termed the mu 1 receptor. The receptor labelled with a mu agonist which possessed a lower affinity they termed the mu 2 receptor. Similarly the receptor labelled with a delta agonist possessing lower affinity for morphine they termed the true delta receptor.It has been postulated that several of the adverse affects including respiratory depression of morphine are due to activation of the mu 2 or lower affinity mu opioid receptor (Pasternak & Wood, 1986). Using this classification it was therefore hypothesised that M6G has a lower affinity for the mu 2 receptor than morphine at least partially explaining the lower apparent toxicity seen in man. The aim of the current study was

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Specificity of opioids towards the μ-, δ- and ϵ-opiate receptors

Cited by 199 publications

References 6 publications

The Relative Potency of Enkephalins and β-Endorphin in Guinea-Pig Ileum, Mouse Vas Deferens and Rat Vas Deferens after the Administration of Peptidase Inhibitors

The Relative Potency of Enkephalins and β-Endorphin in Guinea-Pig Ileum, Mouse Vas Deferens and Rat Vas Deferens after the Administration of Peptidase Inhibitors

60 YEARS OF POMC: Lipotropin and beta-endorphin: a perspective

Explanation at the opioid receptor level for differing toxicity of morphine and morphine 6-glucuronide

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