Colonic Spike Research Articles

The role of opiate receptors and cholinergic neurons in the gastrocolonic response

The aim of this study was to characterize the mechanism of the gastrocolonic response to eating in healthy human volunteers. A bipolar clip electrode recorded spike activity from the distal colon. A rapid increase in colonic spike activity occurred after eating a 1000-cal meal (16.1 ± 2.8 spike potentials/10 min, p < 0.001). The intravenous infusion of atropine inhibited the increase in postprandial colonic motility. Intragastric administration of procaine, a local anesthetic, also inhibited the gastrocolonic response to eating. After sham feeding a modified 1000-cal meal, there was no increase in the gastrocolonic response. Morphine stimulated colonie spike activity (55.3 ± 15.1 spike potentials/10 min, p < 0.001). Naloxone (40 μg/kg · h) completely inhibited morphine stimulation of the colon. Naloxone also inhibited the postprandial gastrocolonic response, but did not inhibit neostigmine stimulation of colonic motility. These data suggest: (1) the gastrocolonic response is mediated by afferent neural receptors in the gastroduodenal mucosa, (2) there is no cephalic phase in the gastrocolonic response to eating, and (3) efferent cholinergic neurons and opiate receptors are both necessary for the gastrocolonic response.

Abnormal colonic motility in progressive systemic sclerosis.

Progressive systemic sclerosis alters smooth muscle function throughout the gastrointestinal tract. In 10 consecutive patients with the disease, colonic spike activity and contractile activity were measured after a 1000-kcal meal, intramuscular injection of neostigmine, or intravenous injection of metoclopramide. The 1000-kcal meal stimulated a significant increase in spike and contractile activity in normal subjects. Nine of the 10 patients had no increase in motility after eating. Neostigmine or metoclopramide stimulated colonic spike (p less than 0.01) and contractile (p less than 0.02) activity in normal subjects and stimulated colonic motility (p less than 0.01) in four of 10 patients with less severe systemic manifestations of the disease (Group 1). The drugs had no effect on patients with severe progressive systemic sclerosis (Group II). The patients with severe scleroderma had significant gastrointestinal roentgenographic abnormalities and severe cardiac, renal, or pulmonary dysfunction. Four of six Group II patients died from the disease; all four had marked smooth muscle atrophy in the colonic wall. These findings suggest that the gastrocolonic response is absent early in the disease process and that the smooth muscle atrophy occurring with progression of the disease may lead to a more severe colonic motor disturbance.

Myoelectric properties of the cat ileocecal sphincter.

Myoelectric activity and intraluminal pressures were recorded simultaneously from the ileum, ileocecal sphincter (ICS), and proximal colon in chloralose-anesthetized cats. Slow-wave activity, seen at all areas, showed coupling of frequency in the distal ileum and ICS. ICS spike activity was both isolated and associated with ileal or colonic spike activity and correlated with phasic contractions (r = 0.86; P less than 0.01). Ileal distensions caused ICS relaxation and decreased spike activity 33.8% of the time. Colonic distensions caused contraction and increased spike activity 46.9% of the time. Migrating action-potential complexes (MAPC) induced by castor oil, ricinoleic acid, or cholecystokinin propagated to the ICS and through to the colon significantly more frequently than ileal non-MAPC (P less than 0.05). Both spike potential-dependent and spike potential-independent mechanisms were involved in ICS contraction. Bethanechol increased spike activity and phasic and tonic contractions. Phenylephrine, despite loss of spike activity in all leads, caused tonic contraction of the ICS. Isoproterenol caused loss of spike activity and decreased ICS pressure. Thus, ICS myoelectric activity appears to be important in determining sphincter function during neurohumoral and mechanical stimulation, with ICS contractions occurring through both a phasic spike-related mechanism and a tonic mechanism without spike activity.

Influence of papaverine on bethanechol or OP-CCK stimulation of feline colonic muscle

Papaverine relaxes smooth muscle from various organ systems throughout the body. The purpose of this study was to determine the effect of papaverine on colonic smooth muscle from the transverse colon of the cat. Myoelectrical activity was recorded with monopolar glass pore electrodes. Papaverine was administered alone and simultaneously with bethanechol or the octapeptide of cholecystokinin. Higher concentrations of papaverine (10−4 M, 10−5 M) abolished both slow-wave activity and migrating spike bursts. Lower concentrations of papaverine (10−6 M) had no effect on slow waves or the migrating spike burst. Bethanechol (10−6 M) or OP-CCK (4 × 10−9 M, 4 × 10−10 M) stimulated spike activity (p < 0.001). Papaverine (10−6 M) completely inhibited the increase in colonic spike activity that was stimulated by bethanechol. Papaverine (10−6 M) had a minimal effect on the increase in spike activity that occurred after octapeptide of cholecystokinin in a concentration of 4 × 10−10 M (p > 0.05). Papaverine had no effect on the stimulation of the colonic smooth muscle by 4 × 10−9 M octapeptide of cholecystokinin. These studies show that (a) papaverine can inhibit smooth muscle myoelectrical activity, (b) papaverine is a potent inhibitor of cholinergic stimulation of colonic smooth muscle, but (c) papaverine has a minimal effect on octapeptide of cholecystokinin stimulation of the isolated colonic smooth muscle.

Colonic dysfunction in diabetes mellitus

Colonic myoelectrical and motor activity were measured in 12 patients with diabetes mellitus. Diabetic patients with severe constipation were compared to diabetics with mild or no constipation. Gastric emptying and peripheral nerve conduction studies were performed in all patients. Normal subjects had a rapid increase in colonic spike and motor activity (P < 0.001) within the first 30-min postprandial period. Diabetic patients with mild constipation had a postprandial increase in colonic motility; however, the response was delayed to 60–90 min after eating. Diabetic patients with severe constipation had no postprandial increase in colonic motility. There was no correlation between colonic motility and gastric emptying of a liquid meal (r = 0.23) (P > 0.05) or peripheral nerve conduction (r = 0.36) (P > 0.05). Neostigmine (0.5 mg, intramuscularly) or metoclopramide (20 mg, intravenously) increased colonic spike (P < 0.005) and motor (P < 0.005) activity in all diabetic subjects regardless of their symptoms. These studies suggest that patients with diabetes mellitus and severe constipation may have an autonomie neuropathy which leads to an absent postprandial gastrocolonic response.

Inhibition of postprandial colonic motility after ingestion of an amino acid mixture.

Previous studies suggested that the ingestion of a mixture of amino acids inhibited the fat-stimulated increase in colonic motility. This study determine the effect of the ingestion of an amino acid mixture on the postprandial distal colonic spike potential (SP) response to a standard 1000-calorie meal in normal subjects and in patients with the irritable bowel syndrome. The distal colonic response was measured following a standard meal with and without the preadministration of a protein hydrolysate solution. After the meal, normal subjects had their maximum response within the first 30-min postprandial period (41.0 +/- 6.3 SP/30 min). Spike activity returned to fasting activity by 60 min. Most patients with irritable bowel syndrome did not have a significant early postprandial distal colonic spike response (P > 0.05), but all patients had a large late increase in spike activity occurring 60-90 min postprandially (50.0 +/- 5.0 SP/30 min) (P < 0.001). Ingestion of the protein hydrolysate solution prior to the meal resulted in suppression of the early colonic spike response in normal subjects (P < 0.01) and the late colonic spike response in the irritable bowel patients (P < 0.01). This study suggests that amino acids can modulate postprandial colonic motility and that dietary alteration may be beneficial in the irritable bowel syndrome.

Abnormal Gastrocolic Response in Patients With Intestinal Pseudo-obstruction

Gastrointestinal motility disturbances after endogenous stimuli have been demonstrated only in the esophagus and small intestine in patients with chronic idiopathic pseudo-obstruction. The 1,000-calorie meal stimulated a significant increase in spike and contractile activity in normal subjects. No increase in colonic spike or contractile activity occurred in patients with chronic idiopathic pseudo-obstruction even though colonic motility increased normally following the administration of neostigmine methylsulfate. These findings suggest that the normal response to eating is absent in patients with chronic idiopathic intestinal pseudo-obstruction even though their smooth muscle has been shown to be responsive to cholinergic stimulation. This loss of a gastrocolic response is further evidence for a disorder of the neurohumoral control mechanisms in patients with chronic idiopathic intestinal pseudo-obstruction.

Origin of high slow-wave frequency in the dog colon.

Using intraparietal and intraluminal electrodes, duodenal and colonic electrical activities were simultaneously recorded in dogs under pentobarbital anaesthesia to study the temporal relationship between the slow-wave frequency of the colon and that of the proximal duodenum. The colonic electromyogram showed two distinct slow-wave frequencies, one in the range of 7-9 cycles/min, and the other in the range of 18-19 cycles/min. The latter was synchronized to that observed on the duodenum, and disappeared after removal of the entire duodenum and the proximal jejunum over 90 cm, from 8 to 98 cm from the pylorus. After transversally cutting the muscular layers of the duodenum at 8 cm from the pylorus, the high slow-wave frequency of the colon decreased to 16-16.5 cycles/min, similarly to that observed on the duodenum aborally to the section. When another section was performed 5 cm aborally to the first cutting level, the colonic slow-wave frequency was again synchronized to that of the duodenum observed aborally to the second section. Intraduodenal infusion of cold water decreased the amplitude of both the duodenal and the colonic slow-waves by 50 p. 100 and the frequency by 30 p. 100. Since all these experimental procedures did not affect the colonic slow-wave frequency at 7-9 cycles/min, and no temporal relationship was found between duodenal and colonic spiking activities, it was concluded that (i) the colonic slow-wave frequency at 18-19 cycles/min, recorded from both the intraparietal and the intraluminal electrodes in dog, was an "artefact" of duodenal activity acting as an electric dipole and (ii) that the only slow-wave frequency of 7-9 cycles/min was generated by the colon.

Effect of bethanechol, gastrin I, or cholecystokinin on myoelectrical activity.

The purpose of this study was to determine the effect of bethanechol, gastrin I, or the octapeptide of cholecystokinin (CCK-OP) on the smooth muscle of the isolated cat colon. Myoelectrical activity was recorded with monopolar glass-pore electrodes. Slow-wave frequency was 5.9 +/- 0.2 cycles/min during the basal period. Slow waves were generally coupled during the control period and the apparent propagation velocity was predominantly aborad at a velocity of 3.8 +/- 0.4 mm/s. Spike activity was superimposed on 11.9 +/- 1.5% of the slow waves during the control period. Bethanechol stimulated a dose-dependent increase in colonic spike activity, with a threshold concentration of 10(-7) M. Bethanechol did not alter the congruence of the colonic slow-wave frequency at any concentration. Gastrin I or CCK-OP increased colonic spike activity. The threshold concentrations for gastrin I and CCK-OP were 2 X 10(-11) M and 4 x 10(-11) M, respectively. Unlike bethanechol, gastrin I (2 X 10(-9) M - 2 X 10(-8) M) and CCK-OP (4 X 10(-9) - 4 X 10(-8) M) altered slow-wave frequency and decreased slow-wave congruence. These studies suggest that 1) bethanechol, gastrin I, or CCK-OP increases colonic spike activity, and 2) only gastrin I or CCK-OP alters the slow-wave frequency of colonic muscle. Thus neurohumoral substances may act independently on colonic spike activity and colonic slow-wave frequency.

Colonic Myoelectrical Activity in Irritable-Bowel Syndrome

To determine the effect of a standard meal on colonic myoelectrical and motor activity in the irritable-bowel syndrome and to determine the effect of a single dose of an oral anticholinergic drug (clidinium bromide) on this response, we studied 10 patients. These patients showed a prolonged increase in both colonic spike (P less than 0.05) and motor activity (P less than 0.05) after eating as compared to normal subjects. Clidinium did not affect the frequency of colonic slow waves or the basal colonic spike and motor activity. However, the anticholinergic reduced the prolonged postprandial colonic spike and motor response in the patients and also reduced the postprandial increase in colonic contractions at 3 cycles per minute (P less than 0.05). These studies indicate that patients with the irritable-bowel syndrome show an abnormally prolonged post-prandial increase in colonic spike and motor activity. An anticholinergic drug reduces the duration and the magnitude of this abnormal colonic response.

Gastrointestinal myoelectrical activity in idiopathic intestinal pseudo-obstruction.

We evaluated the myoelectrical and motor function of the esophagus, small intestine, colon and anal sphincter in four patients with chronic idiopathic intestinal pseudo-obstruction. All patients had aperistalsis of the esophagus, with incomplete relaxation of the lower esophageal sphincter after swallowing or balloon distension. Duodenal slow-wave frequency was normal at 11.4+/-0.3 (+/-S.E.M.) cycles per minute. The patients did not have a normal increase in duodenal spike or motor activity after intestinal distension, but duodenal activity increased after stimulation with intravenous secretin. Colonic slow-wave activities were present at two frequencies, 6.2+/-0.3 and 3.3+/-0.1 cycles per minute. Neostigmine administration increased both colonic spike and motor activity normally. These studies suggest that in this disorder, physiologic neural responses to swallowing or intestinal distension are impaired but the intestinal smooth-muscle slow-wave activity and the spike and motor responses to exogenous neurohormonal stimulation are intact.