Inhibition by Morphine of the Release of Acetylcholine From the Intestine of the Guinea‐pig

Schaumann, W.

doi:10.1111/j.1476-5381.1957.tb01372.x

Cited by 161 publications

(63 citation statements)

References 13 publications

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“…At concentrations of 10-8 to 10-5 M, the drug has been found to depress cholinergic transmission in the smooth muscle of experimental animals (1)(2)(3)(4)(5). At higher concentrations (10-3 to 10-5 M), the same effect was also observed in the skeletal muscle (6)(7)(8).…”

supporting

confidence: 51%

Neuromuscular effects of some opioid agonists and antagonists.

Ramabadran¹,

Lun

1983

Jpn.J.Pharmacol

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Abstract-The effects of morphine, pethidine, (-)naloxone, N-methylnaloxone, naltrex one and levallorphan on acetylcholine-induced contraction of the toad rectus were studied. The drugs were shown to inhibit the contraction, and their inhibitory effect was suggested to be partly mediated via a peripheral opiate binding site. The depression of acetylcholine-induced contraction by levallorphan and dextrallorphan might indicate possible involvement of stereospecific binding sites, as the latter required a significantly higher concentration to produce the same magnitude of depression. Statistical analysis of the slope of the computer-plotted dose-response of acetylcholine in the presence and absence of each of the opioids indicates that these drugs can be classified into four categories. Morphine and naltrexone each formed a class of its own; (-)naloxone, Nmethylnaloxone and pethidine formed another class; levallorphan and dextrallorphan formed the fourth class. The classification of the opioids into four categories reveals the possible existence of multiple opiate binding sites on the skeletal muscle. The significance of each of the sub-types of binding sites in the contraction of skeletal muscle and the mechanism by which it affects the contraction remains to be investigated.

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confidence: 51%

Neuromuscular effects of some opioid agonists and antagonists.

Ramabadran¹,

Lun

1983

Jpn.J.Pharmacol

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“…Morphine inhibits the peristaltic reflex of the guineapig isolated ileum by reducing the output of acetylcholine from the nerves in the myenteric (Auerbach's) plexus which innervate the muscle layers (Schaumann, 1956;1957;Paton, 1957). Localization of the action of morphine to the myenteric plexus neurones was shown by Paton & Zar (1968) by using a preparation which contained only the myenteric plexus and the longitudinal muscle (Rang, 1964).…”

Section: Introductionmentioning

confidence: 99%

The Mechanism of Action of Narcotic Analgesics in the Guinea‐pig Ileum

North

Tonini

1977

British J Pharmacology

126

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Intracellular recordings were made from neurones in the myenteric plexus of the guinea‐pig ileum. Single myenteric ganglia were maintained in vitro and drugs were applied by adding them to the perfusing solution. Narcotic analgesics hyperpolarized the membrane of a proportion of neurones in the myenteric plexus. The membrane hyperpolarization was sometimes associated with a decrease in input resistance. These effects reduced the excitability of myenteric neurones. The effects of narcotics occurred at low concentrations (10 nM to 1 μM), were stereospecific and were reversed by naloxone. It is proposed that the morphine‐sensitive neurones may be the cholinergic efferents to the muscle layers. By hyperpolarizing these neurones, morphine may prevent their excitation by electric field stimulation. This may explain why narcotic analgesics reduce the output of acetylcholine and the contractile response of this preparation when it is excited by field stimulation.

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“…It is interesting to compare the values quoted in the literature for experiments in which eserine or mipafox have been used to allow measurement of spontaneous or electrically-induced release of acetylcholine from the ileum. With eserine, the release of very large quantities of acetylcholine has been reported (Paton, 1957;Schaumann, 1957;Paton, 1963;Ogura et al, 1966;Paton & Zar, 1968). In contrast, when mipafox has been used as an anticholinesterase in similar situations, quantities of acetylcholine some 10-50 times smaller have been obtained (Harry, 1962;Johnson, 1963;Schnieden & Weston, this paper).…”

Section: Discussionmentioning

confidence: 92%

Investigation of the spasmogenic effect of manganese on the guinea‐pig isolated ileum preparation

Schnieden

Weston

1969

British J Pharmacology

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1. The mechanism of the manganese-induced spasm of the guinea-pig ileum was investigated using agents known to modify nerve function. The spasm was reduced by cooling, tetrodotoxin, procaine, Botulinus toxin (Type A), hyoscine and pempidine. It was potentiated by mipafox. 2. In the presence of manganese, the release of acetylcholine from the ileum was greatly increased. 3. Tetrodotoxin prevented the manganese-induced increase in acetylcholine output from the ileum but had no significant effect on the spontaneous acetylcholine output. 4. It is suggested that the manganese-induced spasm of the ileum results from an action on intramural cholinergic nerves.During an investigation of the effect of manganese on the responses of the guineapig isolated ileum preparation to various drugs, it was found that manganese itself, in concentrations ranging from 4 to 64 gM produced a marked spasm of the ileum. This paper presents the results of experiments by which the mechanism of this spasmogenic effect was investigated. A preliminary account of these experiments was communicated to the British Pharmacological Society at the Cardiff Meeting (Schnieden & Weston, 1968). MethodsGuinea-pigs of either sex and weighing 250-450 g were killed by stunning and bleeding. A segment of ileum 2.5 cm in length and situated about 15 cm proximal to the ileo-caecal junction was used. The tissue was set up in a 10 ml. organ bath containing Krebs solution maintained at 370 C and bubbled with a mixture of 95% oxygen and 5% carbon dioxide. Tension changes of the ileum were recorded with a force displacement transducer and pen recorder; the tissue was connected to the transducer with terylene thread.The transducer was supported in a rack work X>block which allowed the resting tension of the ileum to be changed smoothly. The load was initially fixed at 0.5 g but the ileum stretched, lowering the tension in the system. The tissue was washed with Krebs solution at 4 min intervals and the load was adjusted to 0.5 g after each wash. After six to twelve washes, a fairly stable baseline was achieved and the rate of relaxation did not exceed the equivalent of 0.05 g/hr.

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Inhibition by Morphine of the Release of Acetylcholine From the Intestine of the Guinea‐pig

Cited by 161 publications

References 13 publications

Neuromuscular effects of some opioid agonists and antagonists.

Neuromuscular effects of some opioid agonists and antagonists.

The Mechanism of Action of Narcotic Analgesics in the Guinea‐pig Ileum

Investigation of the spasmogenic effect of manganese on the guinea‐pig isolated ileum preparation

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