The actions of caerulein on gastric secretion of the dog and the rat

Abstract

1. Caerulein, as expected from its amino-acid composition and sequence, has a potent stimulant action on gastric secretion in the dog, the rat and the frog. 2. In the denervated fundic pouch of the dog, caerulein increases the rate of flow of gastric juice and the outputs of acid and pepsin. Acid concentration and pepsin concentration in caerulein-produced juice are generally greater than in control juice. The threshold subcutaneous dose of caerulein is 0. 15-0.5 ,ug/kg and the threshold rate of intravenous infusion 0.25-0.5 ,g/kg per hr.Rapid intravenous injection is ineffective. On a molar basis, caerulein is approximately twice as active as human gastrin I on volume and acid output of the gastric pouch and 4 times as active on pepsin output. 3. Sustained acid secretion of the fundic pouch produced by histamine infusion is inhibited by caerulein, administered either intravenously or subcutaneously. In turn, acid secretion elicited by caerulein is inhibited-by atropine. 4. In the rat, the activity ratio of caerulein to human gastrin I is 7-30, calculated on a molar basis, and is thus considerably greater than in the dog. Further, caerulein is 3 times more active than cholecystokinin-pancreozymin. Tested on the perfused stomach preparation of the rat, the threshold dose of caerulein by rapid intravenous injection is 25 ng/kg, by intravenous infusion 0.25 ,ug/kg per hr, and by subcutaneous injection 0.25 to 0.5 ug/kg. 5. The activity of caerulein is sharply reduced by pretreatment of the rats with the histamine liberator 48/80 and potentiated by pretreatment with the diamine oxidase inhibitor aminoguanidine. When caerulein is given by rapid intravenous injection during a priming infusion of histamine its effect is enhanced and considerably prolonged. 6. The isolated mucosa of the frog stomach is extremely sensitive to caerulein which, in a concentration of a few pg/ml., stimulates active transport of chloride.7. Qualitative and quantitative differences in the action of gastrin and caerulein are pointed out, and particular emphasis is laid on the importance of esterification of the tyrosyl residue for the biological activity of caerulein.It was shown in a preceding paper (Bertaccini, De Caro, Endean, Erspamer & Impicciatore, 1968a) that caerulein had a moderate but relatively long-lasting hypotensive action in the dog and the rabbit. A hypotensive action which was less

Gastrin Release by Bombesin in the Dog

“…Previous studies (Bertaccini, Erspamer & Impicciatore, 1973) (Grossman, 1967;Bertaccini, Endean, Erspamer & Impicciatore, 1968). However, increase in plasma gastrin levels remained unchanged or was affected to a much smaller degree.…”

The actions of bombesin on gastric secretion of the dog and the rat

“…Both on a weight and on a molar basis bombesin appeared to be more effective than caerulein which, in its turn, was found to be more potent than human gastrin I (Bertaccini et al, 1968).…”

“…Perfused rat stomach preparation For continuous recording of gastric acid secretion the procedure described by Mantegazza & Piccinini (1962) was followed, slightly modified as described by Bertaccini et al (1968); female rats of the Wistar strain were used.…”

“…The effects of bombesin have been compared with those of caerulein (Bertaccini, Endean, Erspamer & Impicciatore, 1968).…”

Pharmacological Studies of Caerulein

“…The C-terminal sequence of amino acid is the same in caerulein, pancreozymin and gastrins as shown in chemical structures. Therefore, many investi gators have reported that caerulein possesses pancreozymin-like and gastrin-like pharma cological actions (2)(3)(4)(5). However, only a few papers have reported whether or not the actions of caerulein may be partly mediated through the central nervous system.…”