Sensitization of smooth muscle to plasma kinins: effects of enzymes and peptides on various preparations.

1. The influence of various materials, principally hydrolases and peptides, on the sensitivity to stimulating substances has been studied in a wide range of isolated and in vivo smooth muscle preparations.2. Chymotrypsin raised the susceptibility of the guinea-pig isolated ileum to peptides related to bradykinin and also sensitized isolated ileum and fundus of rat and albino gerbil to bradykinin. No sensitization to the kinin occurred in the following preparations: rat, gerbil and rabbit duodenum; rat colon and urinary bladder; dog tracheal chain; and rabbit jejunum. Chymotrypsin and peptides structurally related to the active centre of the enzyme did not affect the permeability increasing property of bradykinin in guinea-pig skin micro-circulation vessels. In contrast, intravenously administered chymotrypsin markedly augmented the bronchoconstrictor action of the kinin.3. Ficin and pronase increased the sensitivity of guinea-pig ileum to bradykinin. Pronase also sensitized the gerbil ileum and this effect was abolished by previous treatment with di-isopropylfluorophosphonate (dyflos). Pronase destroyed bradykinin after incubation.4. Reduced glutathione potentiated the response to bradykinin of guinea-pig ileum but did not affect its sensitivity. The potentiation also occurred in a chymotrypsin-treated preparation.5. It is assumed that specific sensitization elicited by proteinases might derive from an effect on the protein envelope of smooth muscle membrane.