Non-Specific Effects of Synthetic Corticotrophin Polypeptides

Histamine-Releasing Effect of a Corticotrophin Derivative

“…The comparatively very marked histamine-releasing effect of this peptide has already been described in previous papers (8,9,24). Other corticotrophin-like peptides of different chain lengths have been tested for histamine-liberating activity by Jasani and Stanworth (11), who found that the most potent were the 1-24 and 17-26 peptide fragments.…”

“…Jaques (8) and Jaques and Brugger (9) for instance, have reported that these substances -in some cases in very low doses -increase cutaneous vascular permeability in the guinea pig and the rat (8) and when administered intraperitoneally can induce occasionally very marked histamine-releasing effects (9). We have recently demonstrated that tribenoside, the active ingredient of Glyvenol®, can, amongst other things, inhib it the liberation of histamine from isolated peritoneal mast cells of the rat induced by an alkyl-propyl derivative of corticotrophin.…”

On the Paw Oedema Resulting from Subcutaneous Injection of Histamine Liberators in the Rat

“…22, 26[ and has finally led to the discovery of a novel principle of drug action ] 19,21]. In a previous paper it was shown that polypeptides belonging to the corticolrophin group are capable of increasing vascular permeability in the ral skin, regardless of whether or not they possess specific hormonal activity [17]. Such polypeptides have recently been found to liberate histamine in vivo when injected intraperitoneally in the rat: in fact, some alkyl derivatives of these polypeptides proved highly potent liberators inasmuch as a minimal quantity, e.g.…”

Synthetic Polypeptides Related to Corticotrophin Acting as Histamine Liberators

“…A few years ago il was shown that synthetic polypeptides pos sessing amino acid sequences of variable length and chemically related to corticotrophin may produce pronounced increases in vascular permeability in the guinea-pig and the rat as evidenced by leakage of circulating dye or oedema [10]. These effects were observed independently of whether the polypeptide displays ACTH activity or not.…”

“…Thus, for instance, the hormonally fully active ^'■" -corticotrophin ((' .. 30'920-Ba = Synaclhen®) increased vascu lar permeability as effectively as did the /^"'"-corticotrophin frag ment (C. 34'036-Ba) lacking ACTH activity1. II was furthermore shown that the increase in vascular permeability provoked in the rat by /^'"" -corticotrophin was antagonized by anti-inflammatory agents such as sodium salicylate and aminopyrine at compara tively high dosage [10]. In order to characterize the 'prophlogistie' action of /¡'"" -corticotrophin more closely it was decided to examine the polypeptide with regard to its possible activity as a liberator of histamine.…”