Differential sensitivities of morphine and motilin to initiate migrating motor complex in isolated intestinal segments

Matsumoto, Teiji; Sarna, Sushil K.; Condon, Robert E.; Cowles, Verne E.; Frantzides, Constantinos

doi:10.1016/0016-5085(86)90075-2

Cited by 34 publications

(10 citation statements)

References 11 publications

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“…There have been controversial results concerning the effect of motilin on colonic motility in the dog. Motilin did not evoke an excitatory response of the colon (Itoh et al, 1976;Matsumoto et al, 1986;Itoh, 1990), while motilin produced the colonic motor complex (Bickel & Belz, 1988). In contrast, the present results as well as the previous mechanical studies on the rabbit colon in vitro (Satoh et al, 1990;Depoortere et al, 1991;Hasler et al, 1992), have demonstrated that motilin obviously stimulates motor activity of the rabbit colon.…”

Section: Discussioncontrasting

confidence: 60%

“…The dog has been used as a good experimental species for the study of the action of motilin in vivo (Itoh, 1990). It is well known that motilin administered intravenously in dogs causes a series of strong contractions or electrical activity changes corresponding to phase III of the interdigestive migrating motor complex in the gastric antrum and the duodenum without causing simultaneous motility changes in the small intestine, and that the contractions produced migrate through the small intestine towards the terminal ileum (Itoh et al, 1976;Wingate et al, 1976;Matsumoto et al, 1986;Inatomi et al, 1989;Itoh, 1990). The observations in man with motilin are in agreement with the results in dogs (Janssens et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

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Stimulating action of KW‐5139 (Leu¹³‐motilin) on gastrointestinal motility in the rabbit

Kitazawa

Ichikawa

Yokoyama

et al. 1994

British J Pharmacology

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1 The gastrointestinal motor stimulating action of the motilin analogue, , was investigated both in the anaesthetized rabbit and in rabbit isolated smooth muscle tissues. 2 i.v.) produced motor stimulating actions in the gastric antrum, ileum and descending colon, the excitatory responses of which were initiated at the same time but declined with different time courses. The rank order of the excitatory response was: descending colon > gastric antrum >> ileum. 3 Atropine (1-3 mg kg-', i.v.) or naloxone (1 mg kg-', i.v.) completely suppressed the excitatory response to KW-5139 in the gastric antrum, but only partially attenuated that in the descending colon. This suggests that the mechanism of the excitatory response is different in the gastric antrum and the descending colon, and that cholinergic neural pathway is involved in the response of the gastric antrum.4 KW-5139 (0.1 nM-I J1M) caused concentration-dependent contractions of the gastric antrum, duodenum, jejunum, ileum and the descending colon in vitro. In the rabbit intestine, the contractile response to KW-5139 was strongest in the duodenum and weakest in the ileum. 5The contractile response to KW-5139 in the intestinal segments were not affected by tetrodotoxin, but were decreased by verapamil, or pretreatment with a high concentration of porcine motilin, confirming the involvement of motilin receptors in the response to The present results suggest that the rabbit is a suitable species for the investigation of motilin on gut motility, because of the high responsiveness of the descending colon as well as the upper gastrointestinal tract.

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Section: Discussioncontrasting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Stimulating action of KW‐5139 (Leu¹³‐motilin) on gastrointestinal motility in the rabbit

Kitazawa

Ichikawa

Yokoyama

et al. 1994

British J Pharmacology

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“…The higher density of cholinergic nerves in the proximal small intestine (Schulze-Derieu, 1981) could also explain why the motor effects of erythromycin were more pronounced on the proximal small intestine than the distal. However, the differential effect may implicate another receptor system in the light of recent findings that erythromycin competes with the intestinal peptide motilin in binding duodenal receptors (Kondo et al, 1988;Peeters et al, 1989) and that the number and sensivity of these receptor sites are higher in the proximal small bowel (Matsumoto et al, 1986;Bormans et al, 1988;Peeters et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Effects of cholinoceptor and 5‐hydroxytryptamine₃ receptor antagonism on erythromycin‐induced canine intestinal motility disruption and emesis

Qin

Pilot

Thompson

et al. 1993

British J Pharmacology

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1 Erythromycin administration is associated with gastrointestinal problems, disturbed gastrointestinal motility and emesis. This study in the dog investigates the underlying mechanisms. 2 Intestinal myoelectrical activity and the occurrence and latency of emesis were recorded in eight conscious dogs. All drugs were administered intravenously. 3 Erythromycin (7 mg kg-') increased contractions of the proximal small intestine, and caused emesis in all fasted dogs and in 5 dogs after food. Atropine (50 mg kg-' min-') and hexamethonium (10mgkg'lh-') partially inhibited the GI motility effects but did not significantly reduce emesis.4 Metoclopramide at a high dose (2 mg kg-' h-') reduced the incidence of emesis in the presence of increased intestinal motility, but a low dose (15011gkg-'h-') was ineffective. 5 A 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL 72222 (1 mg kg-'), reduced emesis when given alone and combined with metoclopramide (low dose). The 5-HT4 receptor agonist BRL24924 (Renzapride, 1 mg kg-') had no effect on emesis either alone in combination with metoclopramide. 6 In conclusion, erythromycin-induced GI motility disturbances and emesis are not causally related. Whereas the increase in intestinal smooth muscle activity is possibly cholinergically mediated, emesis occurs at least in part via a 5-hydroxytryptaminergic mechanism, but does not involve the dopamine system.

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“…Although gastrointestinal effects may in part be the result of activation of opioid receptors at spinal and supraspinal sites to slow intestinal transit and inhibit secretion, a large body of evidence indicates a direct peripheral activation (Wood and Galligan, 2004). The mechanism of morphine-induced constipation involves inhibition of gastrointestinal peristalsis which occurs as a result of presynaptic inhibition of excitatory cholinergic neurons within the myenteric plexus (Paton, 1957) and may also involve increased tone and non-migrating contractions (Matsumoto et al, 1986; Frantzides et al, 1992). Since the early work of Paton (Paton, 1957), the guinea-pig longitudinal muscle-myenteric plexus (LMPP) preparation has been the tissue preparation of choice to study the in vitro effects of morphine and related opioids in the gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

Morphine Tolerance in the Mouse Ileum and Colon

Ross¹,

Gabra²,

Dewey³

et al. 2008

J Pharmacol Exp Ther

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Repeated administration of morphine is associated with tolerance to its antinociceptive properties. However, constipation remains the major side effect of chronic exposure to morphine. In contrast, previous studies suggest that tolerance to opioids develops in the ileum of several species. In this study, we provide evidence that constipation may arise due to a lack of tolerance development to morphine in the colon. Mice received implants with either placebo or 75 mg of morphine pellets, and they were examined for morphine tolerance to antinociception, defecation, and intestinal and colonic transit after 72 h. Tissues were obtained from the ileum and distal colon, and contractile responses were measured from longitudinal and circular muscle preparations. In morphine-pelleted mice, a 5.5-fold tolerance developed to antinociception after 72 h, and a 53.2-fold tolerance developed in mice that received an additional daily morphine injection. In both models, intestinal transit but not defecation or colonic transit developed tolerance. In isolated longitudinal muscles, electrical field stimulation-induced cholinergic contractions were dose-dependently inhibited by morphine in both the ileum and colon of placebo pelleted with a pD 2 of 7.1 Ϯ 0.4 and 7.8 Ϯ 0.4, respectively. However, the dose response to morphine inhibition was shifted to the right for the ileum from morphine-pelleted mice (pD 2 ϭ 5.1 Ϯ 0.4) but not the colon (pD 2 ϭ 6.9 Ϯ 0.4). In circular muscle preparations, morphine induced atropine-insensitive contractions in both tissue segments. Tolerance to morphine developed in the ileum but not the colon upon repeated administration of morphine. These findings indicate that a lack of tolerance development in the colon is the basis for opioid bowel dysfunction.

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Differential sensitivities of morphine and motilin to initiate migrating motor complex in isolated intestinal segments

Cited by 34 publications

References 11 publications

Stimulating action of KW‐5139 (Leu¹³‐motilin) on gastrointestinal motility in the rabbit

Stimulating action of KW‐5139 (Leu¹³‐motilin) on gastrointestinal motility in the rabbit

Effects of cholinoceptor and 5‐hydroxytryptamine₃ receptor antagonism on erythromycin‐induced canine intestinal motility disruption and emesis

Morphine Tolerance in the Mouse Ileum and Colon

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Differential sensitivities of morphine and motilin to initiate migrating motor complex in isolated intestinal segments

Cited by 34 publications

References 11 publications

Stimulating action of KW‐5139 (Leu13‐motilin) on gastrointestinal motility in the rabbit

Stimulating action of KW‐5139 (Leu13‐motilin) on gastrointestinal motility in the rabbit

Effects of cholinoceptor and 5‐hydroxytryptamine3 receptor antagonism on erythromycin‐induced canine intestinal motility disruption and emesis

Morphine Tolerance in the Mouse Ileum and Colon

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Product

Resources

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Stimulating action of KW‐5139 (Leu¹³‐motilin) on gastrointestinal motility in the rabbit

Stimulating action of KW‐5139 (Leu¹³‐motilin) on gastrointestinal motility in the rabbit

Effects of cholinoceptor and 5‐hydroxytryptamine₃ receptor antagonism on erythromycin‐induced canine intestinal motility disruption and emesis