V.L.W. Go

Human interdigestive and postprandial gastrointestinal motor and gastrointestinal hormone patterns.

Fasting gastrointestinal motor and hormone patterns were studied in 11 healthy volunteers. Cyclic motor activity was present in all subjects during fasting, but the duration and site of onset of each cycle were variable, even in the same subject. Fasting gastrin, GIP, and glucagon levels remained low and constant during the 8-hr study, while plasma motilin levels exhibited cyclic variation in 7 of the 11 subjects. Achlorhydria (induced with cimetidine in 5 of the 11 subjects) did not alter the pattern of fasting motor activity or plasma motilin. In the remaining six subjects, the effect of liquid nutrient meals was examined. Ingestion of a sodium chloride bolus failed to disrupt fasting cyclic activity, while all nutrient-containing solutions inhibited gastric phase-2 motor activity, the duration of inhibition being longest for the mixed and lipid meals. All nutrient meals released GIP, while only protein and mixed meals released gastrin, and the lipid meal released motilin. Our study confirms the rhythmicity of interdigestive motor cycles in man and demonstrates their lack of dependence on gastric acid secretion and some relationship to motilin cycles in certain individuals as determined by radioimmunoassay. Transition from fasting to fed pattern (after liquid meals) is characterized by the inhibition of phasic gastric pressure changes in the antrum and the development of irregular activity in the intestine, similar in pattern to fasting phase 2. Because the duration of interruption of the gastric interdigestive pattern by meals depends on their nutrient content, we conclude that dietary composition may be a major determinant of the fasting-fed motor balance in man.

Relationships among canine fasting pancreatic and biliary secretions, pancreatic duct pressure, and duodenal phase III motor activity--Boldyreff revisited.

Despite the old observations of Boldyreff that pancreatic and biliary secretions occur during periods of intestinal contraction, quantification of these secretions and their relationships to duodenal motor activity and pancreatic ductal pressures have not been reported. By utilizing a recently developed canine model, we simultaneously measured these events. Each of nine dogs was provided with a permanent indwelling pancreatodochal cutaneous catheter (to monitor pancreatic pressure) and three duodenal cutaneous catheters. [14C]PEG was infused through the proximal catheter located in the first part of the duodenum and intraluminal duodenal pressures were monitored through the middle catheter, located at the level of the pancreatic duct orifice. From a third catheter located 15 cm distal to the middle catheter duodenal samples were siphoned, pooled over ice every 15 min, and analyzed for concentration of marker, lipase, and bilirubin. Duodenal volume flows and outputs of lipase and bilirubin were calculated relative to the recovery of the marker. All studies were done in fasting, conscious, upright dogs. Lipase and bilirubin outputs, duodenal volume flow, and mean pancreatic duct pressures increased (P<0.05) during phase III duodenal motor activity, compared with values 15 and 30 min before the onset and after the cessation of phase III motor activity. It is concluded that the inter-digestive housekeeper (phase III motor activity) is comprised of electric, motor, and digestive components. The amount of pancreatic enzymes secreted during phase III activity is 50% of that secreted during a similar time postprandially and is theoretically in sufficient quantity to hydrolyze food remnants and cellular debris. Thus it is likely that the association of increased pancreatic and biliary secretion with intense motor activity of the duodenum render the housekeeping action of the complex more effective.

Vasoactive intestinal polypeptide: a putative transmitter in the canine gastric muscularis mucosa.

The nature of the inhibitory transmitter in the canine gastric muscularis mucosae was studied in vitro using superfusion techniques. The inhibitory effect of nerve stimulation (10 V, 200 mus, 10 Hz) was not altered by adrenergic, cholinergic or serotonergic antagonists. Adenosine triphosphate had no effect on spontaneous mechanical activity. Nucleotide pyrophosphatase and apamin had no effect on the response to nerve stimulation. Alpha‐chymotrypsin abolished the inhibitory effect of nerve stimulation. Radioimmunoassay of the muscle indicated the presence of gastrin/cholecystokinin‐substance P‐ and vasoactive intestinal polypeptide (VIP)‐like immunoreactivity. Of the three peptides present, only VIP produced a concentration‐dependent relaxation. A substance with VIP‐like immunoreactivity was released during nerve‐induced relaxation of the muscle, and its release was blocked by tetrodotoxin and calcium‐depleted solution. The inhibitory effect of nerve stimulation was abolished by VIP antiserum. These data strongly support the hypothesis that VIP or a closely related peptide is an inhibitory neurotransmitter in the canine gastric muscularis mucosae.

Spontaneous contractions and some electrophysiologic properties of circular muscle from normal sigmoid colon and ulcerative colitis.

Spontaneous contractions, inhibitory responses produced by electrical field stimulation, and some electrophysiologic properties of circular smooth muscle from normal sigmoid colon and from sigmoid colon of ulcerative colitis patients were compared in vitro using simultaneous recordings of mechanical and intracellular electrical activity. In normal colonic circular muscle obtained from 21 patients, the frequency of spontaneous summation contractions ranged from 3 to 7 per 4 min, whereas in circular muscle from 13 patients with ulcerative colitis, the frequency of these contractions ranged from 1 to 9 per 4 min. Nonadrenergic, noncholinergic relaxation produced by electrical field stimulation was recorded in the majority of circular smooth muscle strips from both normal colon and colon from patients with ulcerative colitis. There were no significant differences in mean resting membrane potential, mean slow-wave frequency, mean maximum slow-wave amplitude, or inhibitory-junction potential amplitudes recorded using circular smooth muscle from both normal colon and colon from patients with ulcerative colitis. There appeared to be a weak association in patients with ulcerative colitis between increasing duration of symptoms and decreasing frequency of spontaneous summation contractions, but there were no associations between the frequency of these contractions and the severity of colonic inflammation, patient age, or the frequency of stools. The mechanism accounting for a wider range in the frequency of summation contractions recorded from colonic circular smooth muscle in ulcerative colitis remains to be determined.

Dysfunctions of the stomach with gastric ulceration

Factors implicated in the pathogenesis of gastric ulcer were studied simultaneously in seven patients with strictly defined type 1 gastric ulcer (single benign ulcer above the incisura of the stomach) and in six healthy controls. After ingestion of an ordinary solid-liquid meal, patients with gastric ulcer demonstrated gastric hyposecretion of acid, pepsin, and water; delayed gastric emptying of solids with normal emptying of liquids; and increased intragastric concentrations of bile acids. These functional abnormalities appear to be interrelated. Metoclopramide, administered orally in a double-blind fashion, ameliorated the defect in the emptying of solids and the high concentrations of bile acid in the gastric contents. The ability of this drug to break this interdependent cycle suggests the need for further clinical investigation.

Does motilin regulate canine interdigestive gastric motility

Our objective was to determine whether motilin increases the frequency of cyclic interdigestive motor activity in the canine proximal stomach. In 4 conscious dogs with autotransplanted proximal gastric pouches and gastrointestinal electrodes, intravenous infusions or motilin (0.6 μg/kg body wt/hr) increased the frequency of the interdigestive cycles by 30% both in the pouch and in the main gastrointestinal tract. However, the 3-min interval between the end of a cycle in the pouch and the end of a cycle in the duodenum was unchanged by motilin. In control experiments, without motilin infusion, the concentration of endogenous motilin in the plasma during the intense contractile phase of the cycles (overall mean, 385 pg/ml) was greater in each dog (P<0.01) than the concentration during the quiescent phase (overall mean, 256 pg/ml). The concentration of plasma motilin was also greater in the contractile phase (mean, 717 pg/ml) than in the quiescent phase (mean, 587 pg/ml) during exogenous infusions of motilin in two of three dogs (P<0.01). We concluded that motilin increased the frequency of cyclic interdigestive motor activity in the canine proximal stomach and that the increase was not dependent on intact proximal gastric extrinsic innervation.

Postprandial duodenal function in man.

Duodenal function was studied in 11 healthy volunteers after intragastric instillation of a mixed semi-elemental meal. The duodenum accepted chyme of varying pH, osmolality, and nutrient concentration; and, as a result of biliary, pancreatic, and enteric secretion as well as absorption, it delivered chyme with nearly constant pH, osmolality, and nutrient concentration to the jejunum. The flow rate and nutrient load of jejunal chyme varied. The duodenum absorbed more carbohydrate than lipid and less protein, taking up each nutrient at a constant rate during most of the postprandial period. The percentage of nutrient load absorbed was greatest in the late postprandial period, when flow rate, nutrient load, and concentrations were low.

Gastrointestinal Regulatory Peptides Modulate Mouse Lymphocyte Functions Under Serum-Free Conditions In Vitro

Conditions are described for performing mitogen (Concanavalin A, Con A; lipopolysaccharide, LPS) and mixed lymphocyte reaction (MLR) cultures using serum-free medium. The effects of exogenously adding several gastrointestinal regulatory peptides (beta-endorphin, substance P, met-enkephalin, vasoactive intestinal peptide, bombesin and somatostatin) on the incorporation of 3H-methyl-thymidine was determined. It was observed that mitogen stimulation of lymph node cells with Con A was inhibited (70% of control) by vasoactive intestinal peptide (VIP) but spleen cells stimulated by LPS were insensitive to immunomodulation (98% of control). The ability of VIP to inhibit Con A induced thymidine incorporation was concentration dependent (10(-6) to 10(-18) M) and was not attributable to kinetic shifts or cell toxicity. None of the other tested neuropeptides affected Con A or LPS induced blastogenesis. MLR cultures were inhibited by VIP, beta-endorphin and somatostatin in a biphasic manner with maximal inhibition observed at 10(-8) to 10(-12) M. Both substance P and bombesin exhibited slight immunoenhancing properties at 10(-14) to 10(-18) M. Met-enkephalin was ineffective as an immunomodulator of MLR cultures. The utility of using serum-free medium in identifying neuropeptides with immunomodulatory properties are discussed.

Effect of Total Sympathectomy and of Decentralization on Migrating Complexes in Dogs

The effect of total sympathectomy and of decentralization on interdigestive myoelectric activity of the stomach and small intestine and on cycling levels of plasma motilin were studied in conscious dogs. In controls, 98.3% +/- 7.9% of the migrating myoelectric complexes (mean +/- SD) originated in the stomach. In sympathectomized dogs, 38.17% +/- 16.7% originated in the stomach, 35.8% +/- 12.3% in the duodenum, and 26.3% +/- 4.3% in the jejunum. In decentralized dogs, 5.3% +/- 1.4% of the migrating myoelectric complexes originated in the stomach, 71.0% +/- 16.5% in the duodenum, and 23.9% +/- 17.4% in the jejunum. Cycling of plasma motilin was not affected by long-term sympathectomy but coordination of peak levels of plasma motilin and initiation of gastric migrating myoelectric complexes was disrupted in decentralized dogs. These data suggest that central nervous input is required for initiation of migrating myoelectric complexes in the stomach and that central vagal but not central sympathectic input is essential for cycling of plasma motilin.

Motilin regulation of canine interdigestive intestinal motility

The objective was to determine whether motilin regulates cyclical interdigestive motility in the jejunum as well as in the duodenum. In four conscious dogs with an intact innervated duodenum, an autotransplanted (extrinsically denervated) 75-cm loop of proximal jejunum, and an autotransplanted,in situ distal jejunum, interdigestive myoelectrical complexes cycled independently in all three regions of small bowel. Plasma concentration of motilin was greater during phase III of the duodenal cycles (304±37 pg/ml) than during phase I (235±37 pg/ml) or phase II (235±39 pg/ml;P<0.05), but the concentration did not vary consistently with the phases of the cycles in the autotransplanted jejunal segments. Intravenous infusions of motilin (0.6 μg/kg/min for 5 hr), begun 15–30 min after passage of phase III through the duodenum, shortened the interval between phase IIIs in the duodenum from 147±14 min before infusions to 44±3 min during the infusions (P<0.05), but did not alter consistently the interval between phase IIIs in the autotransplanted jejunal segments. Feeding decreased plasma motilin concentration. The data were consistent with motilin regulation of interdigestive motility in intact, innervated canine duodenum but not in extrinsically denervated jejunum.