Active Polypeptides of the Amphibian Skin and Their Synthetic Analogues

Amphibian skin represents an enormous store-house of biogenic amines and active peptides. So far four groups of peptides have been identified: (a) physalaemin-like peptides (physalaemin, phyllomedusin and uperolein) possessing an intense action on vascular and extravascular smooth muscle as well as a potent action on lachrymal and salivary glands. Physalaemin is the most potent hypotensive agent so far described. (b) bradykinin-like peptides (authentic bradykinin, phyllokinin, Val'-Thr5bradykinin) displaying the well known effects on calibre and permeability of the capillaries. (c) caerulein-like peptides (caerulein, phyllocaerulein) reproducing on the smooth muscle of the gall bladder and the gut, and on the exocrine secretions of the stomach, the pancreas, and the liver, all the actions of the intestinal hormone cholecystokinin-pancreozymin. Like this -hormone, caerulein-like peptides also stimulate the secretion of insulin, glucagon and calcitonin. (d) bombesin-like peptides (bombesin, alytesin, ranatensin) possessing a broad spectrum of activity on vascular and extravascular smooth muscle, on gastric acid secretion, and on the kidney, with potent activation of the renin— angiotensin system and stimulation of erythropoietin release. With the exception of uperolein and phyllomedusin all the above peptides have been reproduced by synthesis together with a number of peptides or peptide fragments similar to the natural models. This has permitted some conclusions concerning the problem of structure—activity relationships. Peptides of the amphibian skin are very similar or identical in their structure to active peptides occurring in mammalian tissues (substance P, bradykinins, cholecystokinin, gastrins). Hence their conspicuous interest, transcending the field of comparative pharmacology and biochemistry. It is possible that active amino acid sequences first discovered in amphibian skin may lead to the discovery of similar sequences, i.e. of new biochemical messengers, in mam-