The influence of secretin on the secretion of pepsin in response to acid stimulants in the anaesthetized cat.

Abstract

Peptic secretion was studied in fasting anaesthetized cats in which the pylorus and common bile duct had been occluded to prevent the release of duodenal hormones which might stimulate or inhibit gastric secretion. Dilute acid was instilled into the stomach at intervals to aid recovery of gastric secretion and to preserve peptic activity. 2. Caerulein, histamine and N‐methyl histamine did not increase the output of pepsin when given on their own. Desulphated caerulein was a weak peptic stimulant. 3. Two C.H.R. u./kg per hour secretin initiated pancreatic secretion, the volume of which increased progressively as the dose was increased by stages to 32 C.H.R. u./kg per hour. 4. Four C.H.R. u./kg per hour secretin did not increase the output of pepsin. Peptic secretion was stimulated by 8 C.H.R. u./kg per hour. A maximal output of approximately 2000 u. pepsin/15 min was obtained when 16 C.H.R. u./kg per hour was infused. 5. When each acid stimulant was infused along with 4 C.H.R. u./kg per hour secretin the output of pepsin increased significantly. The peak output, which usually occurred between 15 and 30 min after stimulation, did not exceed 1000 u. pepsin/15 min. 6. The proposed explanation for the potentiation of the peptic response when an acid stimulant is infused along with a dose of secretin, in itself below the threshold of peptic stimulation, is that each acid stimulant increases gastric mucosal blood flow, approximately doubling the effective concentration of secretin delivered to the peptic cell.

A comparison of the pepsin stimulating effects of secretin preparations.

“…At no time did the final concentration of HC1 in the stomach exceed 16 mN and the peptic response was not inhibited by atropine, 1 mg/kg, so that it is unlikely that an acid sensitive cholinergic reflex as suggested by Johnson (1972) was responsible for the increased production of pepsin (Braganza, Gibbs & Howat 1975). The addition of cholic acid in a concentration commonly present in preparations of Boots secretin (T. H. Edmondson, personal communication) also did not enhance peptic secretion (Fig.…”

“…Details of the experimental technique have been described previously (Howat & Schofield, 1954;Braganza, Gibbs & Howat, 1975). In fasting cats, anaesthetized by chloralose (75 mg/kg body wt), the sphlanchnic nerves were sectioned, the pylorus and bile duct occluded and the pancreatic duct cannulated.…”

“…Boots secretin stimulates peptic secretion when infused in doses submaximal for pancreatic stimulation (Braganza, Gibbs & Howat, 1975). One clinical unit (c.u.)…”

The effect of pentagastrin on peptic secretion in man

“…In anaesthetized cats, in which the pylorus was occluded to prevent the release by HCl of a peptic stimulant from the duodenal mucosa, intravenous infusions of caerulein (Braganza, Gibbs & Howat, 1975), gastrin II and pentagastrin (Beswick, Braganza & Howat, 1978, 1979, in doses which stimulated acid secretion submaximally and maximally, did not stimulate the secretion of pepsin. Comparable studies in man are technically difficult since complete but reversible pyloric occlusion is not feasible.…”

Pepsin secretion in anaesthetized cats stimulated by pentagastrin and gastrin II in the presence or absence of secretin.

“…However, these acid stimulants potentiate the peptic response to an infusion of Boots' secretin, itself below the threshold of peptic stimulation, by increasing gastric mucosal blood flow and doubling the effective concentration of secretin delivered to the peptic cell (Braganza, Gibbs & Howat, 1975). Experiments using pentagastrin (t-butyloxycarbonyl-fl-Ala.…”