https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1965.tb02093.x

Observations on an isolated, innervated preparation of rat urinary bladder

/pdf/humoral-factors-affecting-pulmonary-inflation-during-acute-2vs5y8aaya.pdf

Humoral factors affecting pulmonary inflation during acute anaphylaxis in the guinea-pig in vivo.

1. The responses of human cutaneous blood vessels to intradermal injection of bradykinin, histamine and 5-hydroxytryptamine (serotonin) are studied in order to evaluate the ability of these agents to mediate the vascular changes of sustained acute inflammation in the skin.

2. Bradykinin produces erythema, owing to a direct effect on blood vessels, and wealing. Dose—response studies indicate that bradykinin is more potent than serotonin or histamine in respect of wealing.

3. The response to serotonin differs qualitatively as well as quantitatively according to dose. High doses cause wealing and erythema with the characteristics of an axon reflex flare, but low doses produce erythema by a local effect without wealing.

4. Using the technique of arterial occlusion, the occurrence of tachyphylaxis in respect of wealing was demonstrated with histamine and serotonin, but not with bradykinin. This evidence suggests that of the three agents, only bradykinin can mediate increased vascular permeability in sustained acute inflammation.

5. The specificity of tachyphylaxis and the failure of anti-histamine to antagonize bradykinin wealing suggest that bradykinin and histamine act on separate blood vessel receptors.

6. Corticosteroids do not inhibit wealing due to a wide range of doses of bradykinin. The anti-inflammatory activity of corticosteroids may therefore be due to reduced formation of kinins.

Responses of skin blood vessels to bradykinin, histamine and 5-hydroxytryptamine.

Some general effects and the action of eledoisin on a number of isolated smooth muscle preparations have been studied. It has been found that eledoisin possesses a potent stimulating action on all preparations of gastro-intestinal smooth muscle examined and also on the bronchial muscle of the guinea-pig in situ. Preparations of other smooth muscles were less sensitive. The rabbit colon, the guinea-pig ileum and, subordinately, the rabbit uterus and the frog stomach may be profitably used, owing to their sensitivity and the satisfactory dose/response relationship, for the quantitative bioassay of eledoisin in crude or pure preparations of the polypeptide. In parallel assays eledoisin could be easily distinguished from the biogenic amines and from all other known naturally occurring hypotensive polypeptides (bradykinins, wasp kinin, bradykinin-like polypeptides of the amphibian skin, physalaemin, substance P). In the unanaesthetized dog, subcutaneous doses of 25 to 100 μg/kg eledoisin caused a powerful stimulation of the motility and some secretions of the alimentary canal. This effect was much less pronounced in the rat and the rabbit.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1962.tb01198.x

Pharmacological actions of eledoisin on extravascular smooth muscle.

Bovine fibrinopeptide B and human fibrinopeptide A given in minute concentrations to rabbits, dogs, and lambs caused pulmonary hypertension, decreased effective pulmonary blood flow, decreased lung compliance, decreased ventilatory conductance, increased frequency and volume of ventilation, and increased differences in arterial and alveolar Pco2 and Po2. These effects appeared immediately after injection of the peptides into the lesser circulation, increased for 15 to 30 min, and were detectable for as long as 70 min. Mean aortic pressure, heart rate, stroke volume, left and right atrial pressures, and cardiac output showed no systematic changes after injection of these peptides. On the contrary, bovine fibrinopeptide A given in equimolar doses elicited none of the pulmonary responses but induced increases in heart rate, stroke volume, and cardiac output without consistent changes in mean pulmonary or aortic pressure. These responses appeared within 3 min, increased for 5 to 10 min, and disappeared within...

Pulmonary and Circulatory Effects of Fibrinopeptides

The biological activity of synthetic polypeptides containing the amino acids of natural pure trypsin-bradykinin and snake-venom-bradykinin has been investigated. A series of tests for bradykinin-like activity in stimulating plain muscle, depressing the blood pressure and increasing capillary permeability was used on various species. A nonapeptide with the following structure: H-L-Arg-L-Pro-L-Pro-Gly-L-Phe-L-Ser-L-Pro-L-Phe-L-Arg-OH elicited qualitatively and quantitatively the effects of the pure natural bradykinins. An octapeptide with the following structure: H-L-Arg-L-Pro-Gly-L-Phe-L-Ser-L-Pro-L-Phe-L-Arg-OH also exerted bradykinin-like effects but was 50 to 100 times less active than the nonapeptide. Three other octapeptides and a heptapeptide were without any significant effect. Further work will demonstrate if the nonapeptide A is synthetic bradykinin or a peptide with bradykinin-like activity.

Note added since submission of this paper: The data from this investigation were personally precommunicated to Elliott, Lewis, and Horton, who have since found that the structure of pure trypsin-bradykinin is identical with the structure of the nonapeptide A. Therefore, this synthetic nonapeptide is in fact synthetic bradykinin.

E. Stürmer

Papers

Biological activity of synthetic polypeptides with bradykinin-like properties.