M. Impicciatore

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

1 Bombesin stimulated acid secretion from the denervated fundic pouch of the dog. Whereas the concentration of hydrochloric acid in bombesin‐produced juice was always higher than in control juice this did not occur for pepsin, the concentration of which remained below the basal values. The threshold dose of bombesin was 5–30 ng/kg by the subcutaneous route and 0·05–0·2 (μg/kg)/h by intravenous infusion. At low doses bombesin was more active than caerulein, even on a molar basis, and at high dose levels was as active as caerulein. In contrast to gastrin and caerulein, bombesin elicited a moderate secretory response also following rapid intravenous injection. 2 The acid secretion provoked by bombesin was almost completely inhibited by atropine and reduced by approximately 50% by hexamethonium. 3 Bombesin did not stimulate acid secretion in the lumen‐perfused preparation of the rat stomach when administered by subcutaneous injection (up to 10 μg/kg) or by intravenous infusion (up to 10 (μg/kg)/hour). An irregular increase in acid output was observed only following rapid intravenous injection and this was of doubtful significance. 4 The mechanism of the secretagogue action of bombesin on the dog stomach is discussed.

Synthetic peptides related to caerulein. Note 2

Vengono descritte le proprietà di una serie di peptidi sintetici affini alla ceruleina e si discutono brevemente i rapporti fra attività e struttura.

Presence of caerulein in extracts of the skin of Leptodactylus pentadactylus labyrinthicus and of Xenopus laevis

1 The South American amphibian Leptodactylus pentadactylus labyrinthicus and the South African amphibian Xenopus laevis contain in their skin a polypeptide indistinguishable from caerulein prepared from the Australian amphibian Hyla caerulea. 2 The caerulein content of different batches of Leptodactylus pentadactylus labyrinthicus skins varies from 10 to 500–600 μg/g tissue. Drying of the skin causes either a moderate decrease or a slight increase in the caerulein content. Methanol extraction gives considerably higher yields of caerulein than acetone extraction. 3 Caerulein or caerulein‐like polypeptides also occur in the skin of several other species of Leptodactylus together with 5‐hydroxyindole alkylamines and imidazole alkylamines. Yet other species of Leptodactylus lack caerulein‐like polypeptides and 5‐hydroxyindole alkylamines. 4 It is suggested that caerulein and caerulein‐like polypeptides may have some function either in the regulation of secretory processes of the skin or in the exchange of water and electrolytes through the skin, or in both.

Action of caerulein and related substances on the pyloric sphincter of the anaesthetized rat

Abstract The effects of caerulein and related substances on the gastro-duodenal junction of the anaesthetized rat were examined by means of three different techniques. Caerulein appeared to be endowed with a potent spasmogenic action on the pyloric sphincter; the threshold dose was as low as 1–5 ng/kg. The C-terminal octapeptide of cholecystokinin was approximately half as active. Desulphated caerulein retained only 1% of the activity of the mother substance, pentagastrin was twice as active as desulphated caerulein. Secretin had a noticeable spasmogenic activity whereas prostaglandin E1 showed a remarkable spasmolytic effect against the pyloric contraction elicited by caerulein. Results obtained with parasympatholytic and sympatholytic drugs suggested that the activity of caerulein is a ‘direct’ one independent of the autonomic nervous system.

Effects of physalaemin on some exocrine secretions of dogs and rats

1. Physalaemin, an endecapeptide recently found in the skin of the South American amphibian Physalaemus fuscumaculatus, possesses, besides a marked hypotensive action and a powerful sialogogic activity, also a stimulant activity on other exocrine secretions.

Further observations on the spasmogenic activity of caerulein on the rat pylorus.

Summary The contracting activity of caerulein on the gastroduodenal junction of the anaesthetized rat was compared to that of different peptidic and non peptidic spasmogenic compounds. With the exception of phyllocaerulein and bombesin, which were as active as caerulein, all the substances tested were by far less active than the decapeptide. Several drugs were also tested for their ability to antagonize the spasmogenic activity of caerulein on the pyloric sphincter: among these only the sympathomimetic agents were able to inhibit, at relatively low doses, the effect of caerulein. It is suggested that this activity of caerulein may be “physiologically” connected with the stimulant action of biliary and pancreatic secretion.

Pharmacological Data on Caerulein

Caerulein, the active decapeptide which has been detected in our Laboratory in extracts of the skin of the Australian frog Hyla caerulea, is certainly one of the most versatile polypeptides we know so far. In fact, it displays a number of striking pharmacological actions.

Inhibitory effect of intracranial injections of tachykinins on angiotensin-induced drinking in the cat

The tachykinins eledoisin, substance P and kassinin were administered by pulse intracerebroventricular (ICV) injections to cats made thirsty by ICV angiotensin II, 100 ng per cat. Eledoisin, 100 ng per cat, produced an inhibition of drinking which was larger (56.0 vs. 45.2%) and lasted longer than that evoked by 400 ng per cat of substance P. Kassinin, 100 ng per cat, did not evoke any effect at all. The treatment with these peptides neither produced signs of discomfort nor induced any other behavioural alteration. The results of present experiments suggest that the antidipsogenic effect of tachykinins is a phenomenon of general interest among mammals.

Further observations on the insulin stimulating effect of some caerulein-like peptides

Summary Some natural and synthetic caerulein-like peptides were tested in the dog for their ability to stimulate insulin secretion. Most of the compounds examined were less active than caerulein. One natural peptide, namely phyllocaerulein, and one synthetic heptapeptide were found to be 3 and 13 times respectively more potent than caerulein. Structure/activity relationship is discussed and the importance of some amino acid residues and partial sequences is emphasized.