UBC Theses and Dissertations
Fundic inhibition of acid secretion and gastrin release Soon-Shiong, Patrick
Despite earlier indirect evidence that an antral chalone exists, no such inhibitor has been found in antral extract. Recently, interest in the question of an antral inhibitory mechanism has been revived by studies that showed that for a given rise in serum gastrin caused by antral distension, the response of both the innervated and denervated stomach is greatly enhanced by vagal denervation of the antrum. While this study suggested a neuro-humoral character of the antral inhibitory mechanism, it gave no indication as to the source of the inhibitor. Subsequent studies, however, suggested that neither the antrum nor the CNS was the source for this inhibitor. The initial aim of this study was to investigate the fundus as a possible source of the inhibitor by studying the effect of proximal gastric vagotomy on the antral inhibitory mechanism initiated by distension. The results gave clear indication that the inhibitor was indeed released from the fundus; indeed, the antral inhibitory mechanism was in reality a fundic one. Once the fundus was shown to be the source of the inhibitor, it was necessary to establish whether this inhibitor did in fact reside in the fundic mucosa. Four dogs were prepared with a denervated fundic pouch (or Heidenhain pouch, HP), and a fistula of the main, innervated stomach (gastric fistula, GF). The acid secretory responses of both the HP and GF to graded doses of pentagastrin and histamine was studied. In addition both the secretion of acid and the response of immunoreactive gastrin in the blood in response to a standard meal of 15% liver extract was studied. All these experiments were repeated after excision of the fundic mucosa of the main stomach. The results show that excision of the fundic mucosa reduced the GF acid secretion to the stimuli by 85-100%. By contrast, the maximal HP acid secretion increased by 247% in response to pentagastrin and 200% in response to histamine. The increase in the response to submaximal doses of these exogenous stimuli was even greater. Similarly, the peak 30 minutes HP output in response to feeding increased by 418%. Fundic mucosal excision also resulted in the increase in both basal (from 36±3 to 248±37 pg/ml) and food-stimulated response (from 168±12 preoperatively to 392±49 pg/ml postoperatively). Since the intragastric pH was held constant at 5.5 during the meal tests both before and after the operation, the augmented gastrin response could not be attributed to reduced acid secretion caused by excision of the fundic mucosa. From these studies it can be concluded that: (1) antral distension releases an inhibitor from the fundus; (2) excision of the fundic mucosa results in increased response of the HP to both submaximal and maximal doses of pentagastrin and histamine indicating that both the sensitivity of the oxyntic cell and parietal cell mass has increased; (3) excision of the fundic mucosa results in increased basal and food-stimulated gastrin response independent of the pH of the meal suggesting removal of an inhibitor of gastrin release.
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