Inhibitory effect of sulpiride on cinchophen gastric ulceration in dogs

Abstract

An intraventricular administration of sulpiride suppressed the experimental cinchophen ulcer, thereby the effect of repeated administration of the material on cinchophen ulcerogenesis is evident, whereas intermittent administration lacked this effect. Such an effect as reducing experimental cinchophen ulceration, which is due to central neurohumoral mechanism, following intraventricular infusion of sulpiride appears to be ascribable to a chemical blockage of the hypothalamic structure. It can thus be concluded that sulpiride acts principally at the level of hypothalamus. Its inhibitory action on cinchophen gastric ulcer development is probably exerted via the hypothalomo-pituitary-adrenal axis, which is essential to the occurrence of an ulcer, and may be regarded as favoring the central neurohumoral theory of cinchophen ulcerogenesis.

Role of gastric mucosal pepsin in the pathogenesis of acute stress ulceration

“…On the other hand, in patients with chronic gastric ulcer, pepsin concentration in gastric juice was relatively high just before operation, while plasma corticosteroid levels were normal. Previous work by one of us [3] showed that emotional factors associated with anticipation of an operation are capable of increasing the gastric pepsin level and, to a lesser degree, the gastric acid level in patients with chronic peptic ulcer. A further increase in pepsin secretion was observed after abdominal incision in patients with chronic peptic ulcer.…”

“…As soon as the entire mucosal surface pH was determined by the method of Nagamachi and Skoryna [10,11], a section of gastric mucosa was cut away from the underlying submucosa and divided into 1 cm 2 pieces, weighed accurately to the nearest 0.1 g and kept at -20~ until it was homogenized at 0-4~ in 5 ml distilled water. The homogenate was diluted 1 to 50 with 0.01 N HCI, centrifuged (3,000 rpm for 5 minutes), and a quantitative measurement of the peptic activity of fundic mucosal pepsinogen was performed by the same method as used for gastric juice [4,9]. It should be emphasized that similar activities of pepsin have been calculated from mucosa and juice.…”

“…Methods for estimating the histological border zone between the pyloric gland area and fundic gland area (for analyzing the fundic gland mucosal pepsinogen) have been outlined in previous reports [4,[6][7][8]. Plasma l l-hydroxycorticosteroids were measured by the method of Mattingly [12].…”

“…In this condition, fundic ulcerations are common, and no correlation exists with acidity of gastric contents. Previously, we reported that emotional factors, such as those associated with anticipation of an operation, are capable of increasing the plasma corticosteroid levels both in patients with and without chronic peptic ulcers [3], but that a significant increase in acid-peptic activity of gastric juice was observed only in duodenal ulcer patients. Recently, one of us reported studies of cinchophen-induced bleeding and erosion in the fundic gland area and chronic ulcer in the pyloric gland area in dogs [4][5][6][7][8].…”

“…Previously, we reported that emotional factors, such as those associated with anticipation of an operation, are capable of increasing the plasma corticosteroid levels both in patients with and without chronic peptic ulcers [3], but that a significant increase in acid-peptic activity of gastric juice was observed only in duodenal ulcer patients. Recently, one of us reported studies of cinchophen-induced bleeding and erosion in the fundic gland area and chronic ulcer in the pyloric gland area in dogs [4][5][6][7][8]. These studies suggested that intracellular pooled pepsinogen was abnormally high during severe stress associated with high corticosteroid levels, and that this might be a cause of the acute histological changes in the fundic gland mucosa.…”