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PubMed1987

Effects of centrally administered naloxone on gastrointestinal myoelectrical activity in morphine-dependent rats.

The gastrointestinal myoelectrical alterations associated with morphine tolerance and subsequent withdrawal with naloxone were studied before and after treatment with adrenergic blockers, atropine, indomethacin and methysergide administered either i.c.v. or s.c. The rats were prepared chronically with electrodes implanted on the stomach, duodeno-jejunum and colon and two small polyethylene catheters were inserted into the lateral ventricles of the brain. They were rendered physically dependent on morphine by the s.c. administration of a slow-release emulsion containing morphine (75 mg over 48 hr). Morphine treatment was associated with an immediate (15-30 min) inhibition of gastric and colonic spiking activity and intestinal migrating myoelectric complex lasting 6 to 8 hr, followed by a partial recovery of gastric spiking activity while a permanent disorganized motility pattern persisted on the intestine. After 48 hr of morphine treatment the i.c.v. and s.c. administrations of naloxone at doses of 0.03 and 3 mg X kg-1, respectively, promoted typical electrical activity lasting 2 to 3 hr, characterized by the presence of five to seven grouped spike bursts and termed "minute rhythm." Previous central but not peripheral administration of either tolazoline or phentolamine at a dose of 0.3 mg X kg-1 inhibited the i.c.v. naloxone precipitated withdrawal. Neither atropine i.c.v. (30 micrograms X kg-1) nor methysergide i.c.v. (20 micrograms X kg-1) and s.c. (0.2 mg X kg-1) nor indomethacin s.c. (4 mg X kg-1) were found to have any effect on i.c.v. naloxone induced minute rhythm pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Changes in the reactivity of the intrinsic nervous system of the stomach to hexamethonium after transthoracic vagotomy.

Experiments were carried out on seven breedless dogs with chronically implanted electrodes in the stomach. The effect of hexamethonium (in doses of 0.2, 0.3, 0.5, 1, 2, 3, 5, 7 and 10 mg/kg, i. v.) on the migrating myoelectrical complex (MMC) was studied before and after transthoracic vagotomy. Injected on the background of the first MMC phase, hexamethonium in doses of up to 2 mg/kg induces the appearance of spike potentials (SP). Applied on the background of spike activity, hexamethonium induces the appearance of spike activity of the type of the 3rd MMC phase. In a dose exceeding 2 mg/kg, introduced during SP activity, hexamethonium interrupts for different periods of time the SP generation and shortens the duration of the active MMC phases. On the background of increased spike activity characteristic of the stomach after vagotomy, 3 mg/kg hexamethonium have almost no effect on the electrical activity, whereas 10 mg/kg only reduce the percentage of slow waves accompanied by SP. It is probably that after vagotomy the excitability of the intrinsic nerve cells is increased, therefore even the high doses of the ganglionic blocker hexamethonium cannot inhibit entirely the active phases of MMC.

Animals↗

PubMed1985

Effect of alcohol upon myoelectric activity of the gastrointestinal tract and pancreatic and biliary duct pressures.

Myoelectric activity of the antrum, duodenum and sphincter of Oddi was recorded from 12 conscious opossums. The common duct and the pancreatic duct were cannulated for pressure measurements. Recordings were made in the fasted state and after gastric or duodenal administration of ethanol. Alcohol was instilled during phase I (55 experiments) or phase II (ten experiments) of the migrating myoelectric complex. Administration of alcohol caused the appearance of phase III-like activity in five to ten minutes in 91 per cent of the experiments. Pancreatic duct and common duct pressure oscillations occurred synchronously with respiratory movements and with sphincter of Oddi spike potentials. There was an increase in the number of pressure elevations related to the increase in sphincter of Oddi spike potentials after alcohol administration; however, base line pressures remained constant. It is concluded that the administration of alcohol into the stomach or duodenum causes the appearance of phase III-like activity and that there is no change in the base line pressure after the instillation of alcohol.

Animals↗

PubMed1984

Dopaminergic and beta-adrenergic effects on gastric antral motility.

Stimulation of splanchnic nerves and application of adrenergic drugs have been shown to give variable effects on gastric motor activity depending especially on the background activity. beta-adrenoceptors and dopaminergic receptors mediate inhibitory effect on proximal gastric motor activity. The purpose of the present study was to evaluate the effects of isoprenaline, a beta 1- and beta 2-agonist, and dopamine on gastric antral motility in gastric fistula dogs. Dopamine was used alone and in conjunction with selective blockade of adrenergic and dopaminergic receptors during infusion of bethanechol or pentagastrin inducing motor activity patterns as in the phase III of the MMC and the digestive state respectively. The stimulated antral motility was dose-dependently inhibited by dopamine. The effect was significantly blocked by specifically acting dopaminergic blockers, while alpha- and beta-adrenergic blockers were without any significant effects. Dose-response experiments with bethanechol and dopamine showed inhibition of a non-competitive type. Isoprenaline was used alone and in conjunction with selective blockade of beta 1- and beta 2-receptors during infusion of bethanechol which induces a pattern similar to phase III in the migrating myoelectric complex. The stimulated antral motility was dose-dependently inhibited by isoprenaline. The effect could be significantly blocked by propranolol (beta 1 + beta 2-adrenoceptor blocker) and by using in conjunction the beta 1-adrenoceptor blocker practolol and the beta 2-adrenoceptor blocker H 35/25. The dose-response experiments showed inhibition of a non-competitive type. These studies indicate that gastric antral motility is inhibited by isoprenaline through both beta 1- and beta 2-receptors and by dopamine through specific dopaminergic receptors.

Adrenergic beta-Agonists↗

PubMed1984

[The motoricity cycle of the small intestine].

The electrical spike activity of the small intestine at the gastroduodenal junction occurs as migrating myoelectric complexes (MMCs), initiated regularly at intervals of 90-100 min. in the adult sheep and of 20-30 min. in the neonate. This ultradian rhythm, generated by the enteric nervous system, may become identical in the adult and in the neonate, by the use of methysergide which interacts with 5-HT myenteric neurones. The results suggest a postnatal development of a serotoninergic inhibitory system, involved in the control of the basic rest-activity cycle of the small intestine.

5-Hydroxytryptophan↗

PubMed1984

Influence of fasting and bombesin-induced myoelectric activity on the transit of small-intestinal contents in the rat.

The relation between the occurrence of the migrating myoelectric complexes (MMC) and the transit of small-intestinal contents was studied in fasted, conscious rats. MMC were monitored by means of three bipolar electrodes implanted along the small intestine 5, 20, and 35 cm distal to the pylorus. In the presence of an MMC, the radioactive marker was transported along the small intestine as one main peak and recovered aboral to the activity front. Intravenous infusion of bombesin, 3 pmol X kg-1 X min-1, disrupted the MMC and induced irregular spiking activity at all recording levels. Furthermore, during bombesin infusion the radioactive marker was propelled a considerable distance, although the transit was significantly retarded in comparison to that in the presence of an MMC (p less than 0.01). The results indicate that the small-intestinal contents are propelled aboral to an activity front. Continuous irregular spiking activity during bombesin infusion contributes less to the transit of the small-intestinal contents than the activity front of MMC observed during fasting.

Animals↗

PubMed1984

Enhancement of the cyclic motor activity of the ovine small intestine by lysergic acid derivatives. Mechanism and significance.

The effects of a variety of substances influencing the initiation of cyclic motor events at the gastroduodenal junction were studied in conscious sheep. A significant and long-lasting decrease in the frequency of cyclic events from approximately 100 min to 30-40 min was elicited by the intraduodenal bulb administration of the lysergic acid derivatives methylergonovine and methysergide. This effect was dose-dependent and occurred with smaller dosages than those effective when administered parenterally or more distal in the jejunum. Intraluminal administration of cyproheptadine, fonazine, and metergoline into the duodenal bulb increased the interval between phase III activity. At higher dosages, however, cyproheptadine and metergoline reduced the spiking activity of the antroduodenal junction, without significantly changing the cycle duration of the migrating myoelectric complex on the duodenal bulb or jejunum. After administration of cyproheptadine, fonazine, and metergoline, the cycling activity of the duodenojejunum was irregular for 1-2 days. These findings are compatible with a resetting of the enteric biological clock at a faster rhythm and suggest a selective action via an enteric serotoninergic mechanism involved in the normal pacing of the cyclic motor events of the gut.

Action Potentials↗

PubMed1984

Analysis of the control of intestinal motility in fasted rats, with special reference to neurotensin.

Migrating myoelectric complexes (MMC) in the small intestine of fasted rats were monitored by means of four bipolar electrodes chronically implanted at 5, 15, 25, and 35 cm distal to the pylorus. In intact rats the MMC occurred at regular intervals. Truncal abdominal vagotomy did not influence the initiation and propagation of the MMC. Administration of atropine, hexamethonium, or somatostatin significantly decreased the spiking activity of the MMC by 30-45% in the duodenum and jejunum. Infusion of neurotensin at two different doses (3.6 or 7 pmol X kg-1 X min-1) interrupted the activity front of the MMC and induced irregular spiking activity at all recording levels in control rats. In vagotomized rats neurotensin interrupted the activity front inconsistently. After atropine or hexamethonium administration, infusion of neurotensin did not interrupt the distal propagation of the activity front in the jejunum. Guanethidine, naloxone, cimetidine, mepyramine, haloperidol, and a substance P antagonist did not change the MMC or alter the normal response to neurotensin. The results suggest that the inhibitory effect of neurotensin on the propagation of the jejunal activity front involves activation of enteric cholinergic mechanisms. Neurotensin seems to induce irregular spiking activity by a direct myogenic action. The enteric cholinergic innervation of the small intestine partially contributes to the occurrence of the spiking activity of the MMC in fasted rats.

Action Potentials↗

PubMed1984

Effect of 13-norleucin motilin on water and ion transport in the human jejunum.

Passage of the interdigestive migrating myoelectric complex through the proximal small bowel is associated with elevated plasma motilin levels and an increase in transmucosal potential difference suggesting altered ion transport. The aim of the present study was to investigate whether motilin may have an effect on intestinal water and ion transport. Steady state jejunal perfusion studies were carried out in healthy volunteers while either saline (control) or synthetic motilin (256 pmol/kg X h) was infused via peripheral vein. Plasma motilin levels rose from a mean of 31 to a plateau of 832 pmol/L. Motilin infusion significantly reduced absorption of water, sodium, potassium, and chloride when a plasmalike electrolyte solution was perfused. During perfusion with a bicarbonate-free salt solution, motilin significantly enhanced secretion of water, potassium, and chloride. Chloride secretion was active inasmuch as it occurred against both an electrical and chemical gradient. Motilin infusion had no effect on transit time during perfusion of the 30-cm jejunal test segments. We conclude that motilin can act as an intestinal secretagogue in the human jejunum.

Adolescent↗

PubMed1982

[Effect of picomolar intracerebroventricular administration of calcitonin on intestinal motility in the rat (author's transl)].

Intracerebroventricular (ICV) administration of Calcitonin was performed in fed Rats, fitted with chronically implanted electrodes to record the electrical activity of the duodeno-jejunum. At 0.02 u/ICV Calcitonin restored in less than 5 min. the fasted pattern i.e. the migrating myoelectric complex which was previously disrupted by the meal. This effect observed at the lowest dose used (0.083 pmole) required 100 times higher doses by systemic injection and was antagonized by a previous ICV administration of calcium gluconate. It was concluded that Calcitonin is able to suppress the effects of digestive factors responsible for the disruption of the MMC pattern after a meal, this action being related to the ventricular calcium level.

Animals↗

PubMed1982

[Relations between the electric activity of the pyloric sphincter and activities of the stomach and duodenum].

Indwelled electrodes led electrical activity from the stomach, pyloric sphincter and duodenum in hunger, after feeding or administration of carbachol and morphine as well as after transthoracic vagotomy. In intact resting animals the pyloric sphincter develops slow potentials in the rhythm of stomach antral portion and sometimes in the rhythm of duodenum. Acceleration of the slow potentials rhythm occurring after transthoracic vagotomy in the stomach antral portion, develops in the pyloric sphincter as well. Spike activity of the antral portion spreads over to the sphincter depending on amplitude, frequency and duration of the burst of spikes. Migrating myoelectrical complex develops successively in the stomach antral portion and in the pyloric sphincter. During increased activity of the duodenum (after carbachol or morphine) the bursts of spikes in the rhythm of the duodenum slow waves can occur simultaneously in the pyloric sphincter, too.

Animals↗

PubMed1994

[Neurohormonal regulation of gallbladder motility].

The motility of the gallbladder (GB) consists of collection, storage and delivery of bile. GB motor functions are controlled by its extrinsic and intrinsic innervation, and humoral factor. In the fasting stage, GB motility is associated with phase 3 of the interdigestive migrating myoelectric complex and increased plasma motilin concentrations. In the fed state cholecystokinin (CCK) is the primary mediator of GB contraction. Extrinsic neural control of GB motility appears to play a role in the mediation of cephalic phase of GB emptying. Vagal stimulation induces GB concentration, and sympathetic stimulation induces GB relaxation via cholinergic, adrenergic, and noncholinergic, nonadrenergic neurotransmitters. Intrinsic neural control of GB motility is mediated by such neuropeptides as pancreatic polypeptide, somatostatin, bombesin, neuropeptide Y, calcitonin gene-related peptide, vasoactive intestinal polypeptide, CCk, tachykinins and nitric oxide.

Eating↗

PubMed1993

Influence of an abrupt change in diet on antroduodenal myoelectric activity in lactating cattle.

Effects of a change from a diet composed primarily of forage to a diet composed primarily of concentrate on abomasal antral and duodenal motility were assessed in 5 lactating Holstein cows. Antroduodenal motility was measured by use of 8 silver electrodes sutured to the abomasum and duodenum, and abomasal emptying was assessed by continuous measurement of intraduodenal pH. Both diets were fed to achieve a daily dry matter intake of 2.7 kg/100 kg of body weight. The abrupt change in diet did not alter antroduodenal myoelectric activity or abomasal emptying. Initiation of phase III of the migrating myoelectric complex in the proximal portion of the duodenum corresponded with a decrease in abomasal antral spiking activity and an increase in intraduodenal pH. Results suggest that a high concentrate diet alone does not adversely affect antroduodenal motility in adult dairy cattle.

Abomasum↗

PubMed1993

The effect of erythromycin on motility of the duodenum, sphincter of Oddi, and gallbladder in the prairie dog.

BACKGROUND: Interdigestive motility of the stomach, duodenum, sphincter of Oddi, and gallbladder is mediated through the migrating myoelectric complex and the action of motilin. Erythromycin, a motilin agonist, has recently been studied as a gastrointestinal and biliary prokinetic agent. We hypothesized that erythromycin would increase interdigestive duodenal and sphincter of Oddi motility in a dose-dependent manner. METHODS: In 10 anesthetized prairie dogs we determined the motility responses of the duodenum, sphincter of Oddi, and gallbladder to erythromycin infusion during a three-log dosing regimen and correlated activity with serum concentrations of the drug. RESULTS: Erythromycin administered at 0.01 and 0.1 mg/kg had no effect on duodenal or sphincter motility. At 1.0 and 10 mg/kg, duodenal motility index increased by 451% +/- 114% and 1070% +/- 480%, respectively, when compared with baseline values, (p < 0.05). Sphincter of Oddi motility index increased by 122% +/- 38% and 323% +/- 99%, respectively, at these same doses of erythromycin (p < 0.05). Gallbladder pressure did not change significantly during erythromycin infusion. Erythromycin serum concentration at 1.0 mg/kg was 1.0 +/- 0.7 micrograms/ml. CONCLUSIONS: These data suggest that erythromycin stimulates interdigestive motility of the duodenum and sphincter of Oddi in a dose-dependent manner at otherwise subtherapeutic concentrations of the drug.

Animals↗

PubMed1993

[Changes in slow and fast electrical activity of the gastro-duodeno-jejunal junction after cholecystectomy in humans].

The re-establishment of regular gastrointestinal electrical activity (Migrating Myoelectrical Complex-MMC- and slow wave) after cholecystectomy for gallstones was investigated in six female patients (50-77 years) by means of serosal electrodes implanted in the wall of the antrum, duodenum and jejunum during surgery. Five hour recordings were made on the first, third and fifth postoperative days, in patients who were on a liquid diet. The recordings were made after a twelve hour fast. On the fifth postoperative day, a test meal (250 g yoghurt) was given to the patients ant its effects on electrical activity were monitored for 2 hours. Even though MMC were present on the first and third postoperative days, a detailed study of their origin, the length of the Phase 3 and the speed of gastro-jejunal propagation showed that there existed an inhibition of gastric MMC until the fifth postoperative day and that intestinal MMC was slower than normal until the third postoperative day. On the fifth postoperative day, gastric inhibition disappeared since the length of the Phase 3 of the MMC of the stomach corresponds to those of the duodenum and jejunum, and the speed of propagation corresponded to that in normal subjects. Further, the slow wave frequency peculiar to each segment studied increased progressively from the first to the fifth postoperative day and the same was true of the slow waves with superimposed action potentials. In conclusion, notwithstanding the presence of MMC from the first postoperative day, it was only on the fifth day that normal coordination was restored and hence that patients were able to eat again.

Action Potentials↗

PubMed1993

Differential effects of antimuscarinic agents on intestinal motility in the conscious dog.

In this study we investigated the effects of antimuscarinics with different selectivity on the intestinal migrating myoelectric complex (MMC) in five fasting, conscious dogs, chronically fitted with electrodes along the small bowel. Furthermore, we evaluated the chronotropic and mydriatic effects to assess the in vivo selectivity of the agents tested. Dose-response studies were performed with the following drugs administered i.v.: atropine, telenzepine (M1 antagonist), AF-DX 116 [11,2-(diethylamino)methyl-1-piperidinyl-acetyl-5,11-dihydro-6H-pyrido-2 ,3b- 1,4-benzodiazepine-6-one (M2 antagonist)] and 4-diphenylacetoxy-N- methylpiperidine methiodide (4-DAMP) (M3 antagonist). All the antimuscarinics tested dose-dependently increased the duration of the MMC period and inhibited spike activity, except low-dose telenzepine (3-10 nmol/kg), which shortened the MMC period and stimulated spike activity. High-dose telenzepine (> 100 nmol/kg) mimicked the inhibitory effect of atropine on the intestine. ED50 values for delay of MMC onset were 87,232, > 10,000 and 129 nmol/kg for atropine, telenzepine, AF-DX 116 and 4-DAMP, respectively. At doses lengthening the MMC period, atropine and 4-DAMP also induced tachycardia and mydriasis. At doses shortening the MMC period, telenzepine had no effect on pupil diameter or heart rate, except at the dose of 10 nmol/kg, which reduced heart rate. Finally, AF-DX 116, at doses inducing marked tachycardia, had a minor intestinal effect and no mydriatic effect. The present data are consistent with the hypothesis that both M1 and M3 receptors are involved in the regulation of the MMC: M1 receptors are probably located on an inhibitory pathway, whereas M3 receptors mediate excitatory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Comparative action of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs on intestinal motility and nociception in rats.

Central (i.c.v.) effects of D-Tyr-D-Leu-[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(1DME)Y8Fa] and D-Tyr-D-Leu-D-Phe-Gln-Pro-Gln-Arg-Phe-NH2 [(3D)Y8Fa], synthetic analogs of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 on intestinal myoelectric activity and nociception were studied and compared to that of D-Ala2-Met5-enkephalinamide in rats. The duration of disruption of intestinal migrating myoelectric complexes, induced by p.o. administration of a test meal was significantly shortened (P < .01) by (1DME)Y8Fa and (3D)Y8Fa (8, 40 and 80 micrograms/kg) and D-Ala2-Met5-enkephalinamide (40 and 80 micrograms/kg). The coadministration of any two of these drugs, at doses of nonmeasurable effect when given alone (2 micrograms/kg), has also reduced the duration (P < .01) of the postprandial intestinal motor profile. Both separate and combined effects of drugs were antagonized by naloxone (1 mg/kg s.c.). In contrast, in the tail-flick test, analgesia induced by D-Ala2-Met5-enkephalinamide (40 micrograms/kg i.c.v.) was blocked by (1DME)Y8Fa, (3D)Y8Fa (8 micrograms/kg) and naloxone (1 mg/kg s.c.). The coadministration of (1DME)Y8Fa and (3D)Y8Fa at doses of no proper effect when given alone (8 micrograms/kg) has significantly (P < .01) reduced the latency time. This effect was not blocked by naloxone (1 mg/kg s.c.). It is concluded that the Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 analogs, (1DME)Y8Fa and (3D)Y8Fa, when given i.c.v. exert effects similar to opiate agonists and antagonists on intestinal myoelectrical activity and on nociception, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1996

A method for simultaneous recording and assessment of gut contractions and relaxations in vivo.

The normal gut exhibits both contractions and relaxation from a resting tonus. Pathological and pharmacological information may be gleaned from separate measurement of these activities. Methods for recording and analyzing gut contractions have been presented before. We present an extension to the methods, utilising simple foil strain gauges tested here in male Sprague-Dawley rats. Coupled with a computer-based data acquisition and analysis system, we could assess the relaxation and contraction waves recorded simultaneously and from different gut regions in vivo. In contrast with the antrum, where spontaneous motor activity consisted of low frequency relaxations and random contractions, spontaneous duodenal motility was patterned into periodic groups of intense activity interposed by periods of low amplitude, low frequency contractions and relaxations. This grouped activity was propagatory, reminiscent of migrating myoelectrical complexes. When challenged with the ulcerogen cysteamine-HCl (56 mg/100 g s.c.), only duodenal motor activity was affected. Moreover, this treatment had differential effects in the duodenum. Patterned motility was no longer distinguishable, and contraction frequency and amplitude were increased while relaxation amplitude was decreased. This method affords a particularly sensitive and more precise assessment of both contractile and relaxant motor activity in vivo, before and after drug treatment.

Animals↗