A study of tissue fluid removed from regions of local tenderness in the scalp during vascular headache of the migraine type indicated that this fluid contained a painthreshold-lowering substance.4,15 It had many of the properties of vasodilator polypeptides derived from plasma proteins. Armstrong et al.2,3 demonstrated that such polypeptides were present in blister fluid, in fluid collected from painful joints, and in inflammatory pleural fluid. At about the same time, Hilton and Lewis11 described a proteolytic enzyme present in saliva and in saline perfusate of the salivary gland. This enzyme formed vasodilator polypeptides when incubated with plasma proteins. Increased amounts of enzyme were observed during heightened metabolic activity of the gland. Hilton and Lewis concluded that the enzyme and polypeptide are responsible for local vasomotor control in the salivary gland. The properties of the polypeptide correspond closely to those of "bradykinin," the name given by Rocha e
CHAPMAN LF, WOLFF HG. Studies of Proteolytic Enzymes in Cerebrospinal Fluid: Capacity of Incubated Mixtures of Cerebrospinal Fluid and Plasma Proteins to Form Vasodilator Substances That Contract the Isolated Rat Uterus. AMA Arch Intern Med. 1959;103(1):86–94. doi:10.1001/archinte.1959.00270010092012
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