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

Huidobro, F; Huidobro‐Toro, J. Pablo; Miranda, Hugo F.

doi:10.1111/j.1476-5381.1980.tb09770.x

Cited by 26 publications

(6 citation statements)

References 12 publications

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“…Indeed, in the rat colon, P-endorphin is about 10 times more potent than morphine and about 3 times as potent as the enkephalins. These results are in decided contrast to the relative ratio of potency of these agents as compared to that of morphine in the guinea-pig ileum, mouse or rat vas deferens (Lord et al, 1977;Wuster, Schulz & Herz, 1979;Huidobro, Huidobro-Toro & Miranda, 1980;.…”

Section: Discussioncontrasting

confidence: 46%

Contractile Effect of Morphine and Related Opioid Alkaloids, Β‐endorphin and Methionine Enkephalin on the Isolated Colon From Long Evans Rats

Huidobro‐Toro

Way

1981

British J Pharmacology

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1 Morphine and related synthetic surrogates as well as P-endorphin and methionine enkephalin caused a contractile response of the longitudinal musculature of the terminal colon of Long Evans rats. 2 The muscular contraction caused by the narcotic analgesics exhibited stereospecificity, with levorphanol being about 50 times more potent than dextrorphan and (-)-methadone 4 times more potent than (+ )-methadone. In addition, the rank order in potency of a homologous series of N-alkyl substituted norketobemidones demonstrated that the activity of these compounds in eliciting contractile responses corresponded to that for analgesic efficacy in the rat and also correlated to the ability of these derivatives to inhibit the muscular twitch evoked by electrical stimulation of the guinea-pig ileum. 3 Naloxone blocked the contractile response of the opiates following competitive kinetics; the naloxone pA2 values for morphine, etorphine, levorphanol and methadone were very close, in spite of the marked differences in potency of these agents. 4 The contractile effect of morphine on the rat colon was abolished by incubation of the tissues with tetrodotoxin 2.0 x 10-7M or by decreasing the external Ca2+ level 100 fold. Increasing the external Ca2+ concentration caused an apparent non-competitive antagonism of the response to morphine. 5 Pretreatment of the tissues with hexamethonium 8.3 x 10-5M caused a modest antagonism of the morphine effect while atropine 5.8 x 10-7M did not significantly modify the morphine contractile effect. In contrast, methysergide 1i-5 M caused a 10 fold increase in the morphine EC50.6 Colons from rats rendered tolerant-dependent on morphine were markedly less sensitive to the contractile effects of morphine than those from placebo-treated controls. Tolerance to morphine was also accompanied by an increased sensitivity to the contractile effects of 5-hydroxytryptamine (5-HT).7 A marked increase in the spontaneous muscular activity of segments of the terminal colon of rats chronically treated with morphine was found to occur upon removal of the residual morphine in the tissues by repetitive washings. The spontaneous activity was arrested by applications of morphine, suggesting that physical dependence can be demonstrated in vitro in this particular preparation. 8 It is concluded that the opiate-induced contractile response is mediated via stereospecific, naloxone-sensitive, opiate receptors and that the muscular response involves the activation of a 5-HT neurone in the nerve terminals of the colon.

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Section: Discussioncontrasting

confidence: 46%

Contractile Effect of Morphine and Related Opioid Alkaloids, Β‐endorphin and Methionine Enkephalin on the Isolated Colon From Long Evans Rats

Huidobro‐Toro

Way

1981

British J Pharmacology

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“…The K, values of naloxone against dynorphin-(1-13) and a-neo-endorphin obtained in the present experiments (see Table 2) were close to that obtained in the guinea-pig ileum with K-receptor agonists. Furthermore, in the guinea-pig oesophagus, morphine acts as a partial agonist, as the drug does in the rat vas deferens (Huidobro, Huidobro-Toro & Miranda, 1980;Ishii, Yamamoto, Muraki & Kato, 1981).…”

Section: Discussionmentioning

confidence: 98%

Pharmacological characterization of the opioid receptor in the submucous plexus of the guinea‐pig oesophagus

Kamikawa

Shimo

1983

British J Pharmacology

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1 The cholinergically mediated electrically-induced contractions of the submucous plexuslongitudinal muscularis mucosae preparation of the guinea-pig oesophagus were used to study the actions of opioid peptides and morphine. 2 The twitch contractions of the tissue (0.1 Hz, 0.5m s, supramaximal voltage) were inhibited by all the opioid peptides and morphine in a concentration-dependent manner. The order of potency was dynorphin-(1-13) > a-neo-endorphin > P-endorphin > [D-Ala2]-methionine-enkephalin >> aendorphin, methionine-enkephalin, leucine-enkephalin and morphine.3 The inhibitory actions of dynorphin-(1-13) (20 nM), cx-neo-endorphin (100 nM) and Pendorphin (3 jiM) were completely reversed either by naloxone (1 jiM) or by morphine (100 jiM). The Ke values of naloxone against dynorphin-(1-13) and a-neo-endorphin were 30 and 25 nm, respectively. 4 Increasing the concentration of calcium from 1.8 to 3.6 mM in Tyrode solution decreased the sensitivity of the tissue to dynorphin-(1-13) 7.4 times and to x-neo-endorphin 462 times. 5 The inhibitory actions of dynorphin-(1-13) (100nM) and ac-neo-endorphin (300nM) were inversely related to stimulus frequency, being most active at low frequencies (0.1-1 Hz), and least active at high (30 Hz). 6 Exogenously applied acetylcholine produced concentration-dependent contractions of the isolated muscularis mucosae, with an EC50 of 72.6±4.5nM. The contractile response of the oesophagus to acetylcholine was not affected by the pretreatment of the tissue with dynorphin-(1-13) (100 nM), a-neo-endorphin (300 nM) or P-endorphin (3 JiM).7 It is concluded that the submucous plexus-longitudinal muscularis mucosae of the guinea-pig oesophagus is inhibited by opioid peptides acting at prejunctional opioid receptors, probably of the K-subtype.

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“…(12) reported that morphine acted as an antagonist on the inhibitory effect of Q-endorphin in the isolated vas deferens from naive rats.…”

Section: Discussionmentioning

confidence: 99%

Partial agonistic action of morphine in the rat vas deferens.

et al. 1981

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

Cited by 26 publications

References 12 publications

Contractile Effect of Morphine and Related Opioid Alkaloids, Β‐endorphin and Methionine Enkephalin on the Isolated Colon From Long Evans Rats

Contractile Effect of Morphine and Related Opioid Alkaloids, Β‐endorphin and Methionine Enkephalin on the Isolated Colon From Long Evans Rats

Pharmacological characterization of the opioid receptor in the submucous plexus of the guinea‐pig oesophagus

Partial agonistic action of morphine in the rat vas deferens.

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