In vitro pharmacology of the opioid peptides, enkephalins and endorphins

Waterfield, Angela A.; Smokcum, Roger W.J.; Hughes, J.; Kosterlitz, H. W.; Henderson, Graeme

doi:10.1016/0014-2999(77)90123-6

Cited by 201 publications

(34 citation statements)

References 17 publications

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“…One type of opiate receptor is apparently specific for the opioid-like peptides. This receptor is similar to that activated by the endogenous opioids in the guinea-pig ileum (Waterfield, Smockum, Hughes, Kosterlitz & Henderson, 1977;Huidobro-Toro, Foree & Way, 1978), and the mouse vas deferens (Hughes, Smith, Kosterlitz, Fothergill, Morgan & Morris, 1975). The other receptor site, activated by morphine and surrogates shows a low degree of stereospecificity, develops tolerance to the effect of chronic morphine, but the responses are not blocked by naloxone.…”

Section: Discussionmentioning

confidence: 62%

Interactions Between Morphine and the Opioid‐like Peptides in the Rat Vas Deferens

Huidobro

Huidobro‐Toro

Miranda

1980

British J Pharmacology

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1 Morphine, methadone, levorphanol, pethidine, etonitazene and related morphine-like alkaloids produced an increase in the electrically-evoked muscular contraction of the rat vas deferens. In contrast, the enkephalins and f-endorphin caused inhibition of the twitching.2 The concentration of fi-endorphin required to inhibit by 50% the muscular twitch was about 50 to 100 times less than that of the enkephalins. 3 Pretreatment of the vasa with morphine antagonized the inhibition of the neuromuscular transmission caused by either P-endorphin or enkephalin. 4 Conversely, pretreatment with P-endorphin sensitized the vasa to the increase in twitch tension caused by morphine. 5 Morphine did not alter the sensitivity to exogenously administered noradrenaline, dopamine or potassium.

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Section: Discussionmentioning

confidence: 62%

Interactions Between Morphine and the Opioid‐like Peptides in the Rat Vas Deferens

Huidobro

Huidobro‐Toro

Miranda

1980

British J Pharmacology

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“…Etorphine, an oripavine narcotic, appears to have high affinity for both 3 and ,t receptors (25). In addition, the related antagonist, diprenorphine, appears more effective than naloxone as an antagonist in the mouse vas deferens (26 …”

Section: Resultsmentioning

confidence: 97%

Control of guinea pig intestinal electrolyte secretion by a delta-opiate receptor.

Kachur

Miller

Field

1980

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

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The effects of opioids on transepithelial potential difference and short-circuit current across guinea pig ileum stripped of one muscle layer were measured in vitro in Ussing chambers. Opioid peptides such as [DA6a2, DMet5Jenkephalin, which are primarily agonists at -opiate receptors, were able to reduce transepithelial potential difference and short-circuit current at concentrations as low as 1 nM. The narcotic drug etorphine was also very potent in reducing short-circuit current, but fentanyl and morphine, which are primarily agonists at -opiate receptors, were almost complete y ineffective. Ketocyclazocine was relatively ineffective, and P-endorphin had intermediate potency.All opioid effects could be reversed by the opiate antagonist naloxone. Somatostatin also reduced short-circuit current, but its effect was not reduced by naloxone. Chloride flux measurements indicated that the effect of etorphine on short-Circuit current is associated with an enhancement of active Cl-absorption. The relative effects of opioids in this system suggest that their actions are being mediated by a specific 5-opiate receptor. In contrast, opioid effects on guinea pig intestinal smooth muscle seem to be primarily mediated by a i-opiate receptor.Opiates and opiate-like drugs such as diphenoxylate and loperamide are widely used in the treatment of diarrhea (1-4). Opiates are generally believed to produce their antidiarrheal action by stimulating intestinal circular muscle, thereby impeding the progress of material through the gut (5-7). In addition, in the guinea pig myenteric plexus, opioids also decrease the stimulated release of acetylcholine from cholinergic neurons. This action is the basis for a well established pharmacological assay for opiates (8). The recent discovery of the endogenous opioid peptides, the enkephalins, has provided a neuroanatomical basis for much of the classical pharmacology of the opiates (9). In particular, both [Met5]enkephalin and [Leu5]enkephalin have been found in intestinal enteric ganglia and in endocrine cells of the gut mucosa, suggesting a physiological role for the enkephalins in the gastrointestinal tract (10-12). One possibility is that they act as neurotransmitters and influence intestinal motility. Another possibility is that the enkephalins may have "paracrine" effects on the intestinal mucosa. Enkephalin released locally from endocrine cells or neuronal elements might act upon the intestinal mucosa to regulate the release of other bioactive substances or, more directly, the transport of ions across the mucosa. We have recently demonstrated that somatostatin may modulate electrolyte transport across rabbit ileal mucosa (13). The present paper demonstrates that opioids have an antisecretory effect on guinea pig mucosa. At the present time there is considerable discussion as to the possible existence of multiple opiate receptors. This would be analogous to the situation with acetylcholine, for example, where both nicotinic and muscarinic types of receptors The publication costs ...

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“…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%

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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In vitro pharmacology of the opioid peptides, enkephalins and endorphins

Cited by 201 publications

References 17 publications

Interactions Between Morphine and the Opioid‐like Peptides in the Rat Vas Deferens

Interactions Between Morphine and the Opioid‐like Peptides in the Rat Vas Deferens

Control of guinea pig intestinal electrolyte secretion by a delta-opiate receptor.

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

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