Effects of histamine on the lower esophageal sphincter in vivo: evidence for action at three different sites.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R K Goyal.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Studies were performed in anesthetized opossums to investigate the electrical activity that may characterize the lower esophageal sphincter. The stomach and lower end of the esophagus were immobilized on a specially prepared stage to eliminate movement artifacts. Extracellular electrical activity was recorded with bipolar needle electrodes. The sphincter pressure was measured with a continuously perfused catheter system. The lower esophageal sphincter showed continuous spike activity with or without phasic variations in their occurrence. The usual frequency of the spikes was 20 to 50 per min, and their duration was 81.2 +/- 8.9 msec (mean +/- SE). The spike potentials ceased with esophageal distention, which also caused a fall in the sphincter pressure. The spikes were abolished by isoproterenol and they increased with bethanechol. Correlation of the spike activity with the pressure revealed that the sphincter pressure was higher when the spike potentials were present, but a major part of the pressure existed in the absence of any spike activity. These studies show that: (1) the oppossum lower esophageal sphincter is characterized by continuous spike potentials, and (2) the major fraction of the basal pressure is, however, independent of the spike potentials.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Tissue gastrin was determined in 36 biopsies obtained from the esophagus and 35 biopsies from the stomach in 12 patients with Barrett's esophagus. Histology of the mucosa from the area adjacent to the biopsy sites was also examined. Esophageal biopsies were obtained from three different sites in each patient. The gastric biopsies were obtained from the antrum, fundus, and the area just distal to the lower border of the lower esophageal sphincter. The columnar mucosa lining the esophagus was of three distinct types, namely, fundic, transitional (cardiac), or specialized. None of these epithelia nor the squamous epithelium showed any detectable gastrin. In contrast, antral mucosa had very high gastrin content; smaller amounts of gastrin were detected in duodenal epithelium, whereas fundic mucosa sometimes contained small amounts of gastrin.
Intravenous administration of 5-hydroxytryptamine (5-HT) caused a dose-dependent contraction in the lower esophageal sphincter in the opossum. The smallest dose of 5-HT which caused a detectable contraction of the sphincter was 0.5 mug/kg, and a maximal sphincter contraction was produced by a dose of 40 mug/kg. Methysergide converted the contractile effect of 5-HT to a dose-dependent fall in the sphincter pressure; maximal inhibition of 77.2 +/- 7.2% of the resting pressure occurred with a dose of 40 mug/kg. The inhibitory effect of 5-HT was antagonized by tetrodotoxin, 5 MeO-DMT, and 5-HT tachyphylaxis. 5 MeO-DMT enhanced 5-HT-induced contraction of the sphincter. In the presence of 5 MeO-DMT and methysergide, 5-HT still caused a brief contraction of the sphincter; this contraction appeared to be due to stimulation of postganglionic cholinergic neurons as it was antagonized by tetrodotoxin or atropine. Reserpinization caused enhancement of the sphincter contraction by 5-HT. In the reserpinized animals in the presence of methysergide, 5-HT caused a small initial contraction followed by prolonged inhibition; atropine antagonized the initial contraction, while inhibition was antagonized by 5 MeO-DMT. These studies are consistent with the view that 5-HT exerts several different effects on the sphincter. 5-HT causes contraction of the sphincter by its direct action on the muscle and also by stimulation of cholinergic excitatory neurons. In addition, 5-HT inhibits the sphincter by stimulation of nonadrenergic inhibitory neurons.
Variations in the counts of circulating basophile leucocytes in 225 subjects were studied. The results obtained are as follows: 1) The counts (per mm3) show a gradual rise with growth, from infancy to adolescence, and maintain a fair constancy in adults. 2) No significant sex difference was found in the peripheral basophile counts. 3) A definite diurnal variation in the counts exists, which is lowest in the morning and highest in the evening. 4) the counts are altered in different phases of the menstrual cycle. 5) Pregnant women show lower counts than nonpregnant women. 6) Surgical trauma and a single electroconvulsive shock lowers the counts significantly but variations are not significant after meals and physical exercise. 7) Smokers have slightly higher counts than non-smokers. 8) course of irradiation therapy lowers the counts significantly in patients with inoperable noplastic diseases. 9) Counts show insignificant variation with alteration of blood glucose level. The results mentioned above are discussed.
Explore the source record for details and available documents.
To define the histology of the columnarlined esophagus, we obtained esophageal biopsies from various levels with manometric control from 11 patients. There were three types of columnar epithelia above the lower esophageal sphincter: atrophic gastric-fundic-type epithelium with parietal and chief cells; junctional-type epithelium with cardiac mucous glands; and distinctive specialized columnar epithelium with a villiform surface, mucous glands and intestinal-type goblet cells. When present, specialized columnar epithelium was always the most proximal, and gastric fundic epithelium the most distal epithelium. Junctional epithelium was interposed between gastric fundic and specialized columnar or squamous epithelium. Four patients had unequivocal esophagitis in squamous epithelium, but its presence and severity did not correlate with inflammation in or length or type of distal columnar epithelium. Histoligic study of the columnar-lined esophagus demonstrated a spectrum of epithelial patterns. This heterogeneity helps to explain prior discrepant reports.
Explore the source record for details and available documents.
Dose-response curves for the effect of continuous infusion of histamine on gastric acid secretion were obtained in 10 patients with iron deficiency anemia due to hookworm infection. Each patient was studied with 4 doses (40, 60, 80 and 100 mug/kg/h) of histamine acid phosphate administered for 3 h, on separate days, in random fashion. The acid output increased with the dose of histamine, the maximal acid output was reached in all patients at the dose of 100 mug/kg/h. The dose of histamine when calculated according to body weight correlated well with the maximal acid output; the absolute dose of histamine had no correlation with the maximal acid response. The dose-response curve of stimulated acid output in anemia patients was much flatter than in control patients.
Studies were performed in anesthetized opossums to determine the influence of binding of circulating gastrin with a high titer gastrin antiserum on lower esophageal sphincter pressure. Gastrin antiserum or control antiserum was administered intravenously in successive doses of 0.02, 0.1, and 0.5 ml/kg on separate days. The lower esophageal sphincter pressures were measured for 1 h before and for 1 h after antiserum administration. The control serum caused no binding of opossum circulating gastrin, nor did it modify lower esophageal sphincter pressure. On the other hand, the administration of gastrin antiserum resulted in the binding of 85-90% of circulating gastrin, but it did not reduce sphincter pressure. A continuous infusion of 0.25 mug-kg-1-h-1 of synthetic human gastrin I caused a significant (P less than 0.05) increase in the sphincter pressure, a 30-fold increase in gastric acid output, and a fourfold increase in immunoreactive gastrin in the opossum blood. Prior treatment with 0.1 ml/kg of gastrin antiserum antagonized and 0.2 ml/kg of the antiserum abolished the gastrin-stimulated gastric acid secretion and the stimulating effect of gastrin on lower esophageal sphincter pressure. However, neither dose of antiserum modified basal lower esophageal sphincter pressure. It is concluded that circulating gastrin may be an important determinant of basal sphincter pressure.
The absolute counts on basophil and eosinophil leucocytes, percentage of vacuolated eosinophil cells and whole blood histamine were determined in 30 controls and 34 patients with bronchial asthma. The basophil counts rose from the quiescent to pre-attack stage and then fell in the acute stage of bronchial asthma. The eosinophil counts, the percentage of vacuolated eosinophils and the blood histamine content increased significantly during an asthmatic attack. An attack of bronchial asthma was precipitated if the blood histamine rose to or above 200 ng/ml or a 50% rise occurred from its quiescent level. The inter-relationship between cytomorphological variations and blood histamine content in various stages of bronchial asthma is discussed.
Gastrin I or pentagastrin caused contraction of the lowe esophageal sphincter in anesthetized oppossums. The contraction was not modified, either qualitatively or quantitatively, by 30 or 1000 mug per kg atropine pretreatment. Moreover, neural block with tetrodotoxin did not influence the effect of gastrin on the sphincter pressure. H2 receptor antagonist, metiamide, did not modify the magnitude of the contractile response of the lower esophageal sphincter to gastrin I. These studies show: a) gastrin does not cause sphincter contraction by stimulating cholinergic neurons: and b) gastrin does not exert an inhibitory effect on the sponcter pressure by stimulating H2 receptors. We suggest that gastrin may contract the lower esophageal sphincter by a direct action on the sphincter muscle.
Currently it is believed that lower esophageal sphincter closure is maintained by tonic neurohormonal activity. Studies were performed to evaluate the role of neural and myogenic activity in the genesis of resting sphincter pressure in the opossum. The neural activity in the sphincter was blocked by intravenous administration of the puffer fish poison, tetrodotoxin, in intact animals. The respiration in these animals was assisted with a respirator, their blood pressure was supported by intravenous administration of Ringer's solution, and their body temperature was maintained by heating lamp. The lower esophageal sphincter pressures were measured with water-filled and continuously perfused catheters which were anchored to the lower esophageal sphincter using a new technique. Tetrodotoxin blocked the sphincter response to neural stimulation with vagal stimulation, esophageal distention, and local electrical stimulation of the sphincter. The mean resting sphincter pressure before tetrodotoxin was 59.0 +/- 2.6 mm Hg, and it was 64.4 +/- 6.9 mm Hg after tetrodotoxin (P greater than 0.05). During neural block with tetrodotoxin, the sphincter response to administration of isoproterenol or bethanechol was similar to that during the control period (P greater than 0.05). These studies show that: (1) Tetrodotoxin can be administered in intact animals to achieve complete block of neural activity in the lower esophageal sphincter; (2) sphincter muscle is not adversely affected by tetrodotoxin; and (3) block of neural activity does not alter the resting lower esophageal sphincter pressure.
Explore the source record for details and available documents.
Intravenous administration of dopamine caused a dose-dependent reduction in the lower esophageal sphincter pressure and contractions in the lowermost part of the body of the esophagus in the opossum. A dose of 5 mug per kg produced maximal response. The onset of contractions in the body occurred around 20 sec after the onset of the sphincter response. The effect of dopamine was different from isoproterenol, which caused no contractions in the body and caused reduction in sphincter pressure, and from phenylephrine, which also caused no contractions in the body but caused contraction of the sphincter. Moreover, the effect of 5 mug per kg of dopamine was blocked by haloperidol but not by phentolamine, propranolol, bilateral cervical vagotomy, or tetrodotoxin. These studies suggested the presence of selective dopamine receptors which mediated contraction of the esophageal body and relaxation of the sphincter muscle. Since vagal stimulation also causes contraction in the body and relaxation of the sphincter, it was possible that vagal effect on the esophagus was mediated by dopamine receptors. However, haloperidol did not block the effect of electrical stimulation of vagus nerve on body of the esophagus or the lower esophageal sphincter.