The Pharmacology of Chymotrypsin Administered by Inhalation

Abstract

The ability of chymotrypsin to reach the limits of the bronchial tree has been studied in cats receiving the enzyme by inhalation as a very fine powder. For this purpose derivatives of chymotrypsin were used which had been labelled with a fluorescent molecule or with [1311].Quantitative measurements of the absorption and distribution of inhaled chymotrypsin-[131I] revealed a rapid removal of radioactivity from the lungs over the first 24 hr. and corresponding excretion of labelled inorganic iodide in the urine. High levels of activity were not attained in the blood or thyroid. Subcutaneous administration of labelled enzyme led to more rapid accumulation of radioactivity in the blood and thyroid. Consideration of these and other results leads to the conclusion that, while some enzyme ascends the respiratory tract by ciliary movement of mucus, a substantial part is absorbed into the lungs and the [1311] subsequently detached from it.The changes in tidal air accompanying inhalation of labelled trypsin and chymotrypsin were followed in anaesthetized cats. Trypsin brings about a decrease in tidal air in distinctly lower doses than does chymotrypsin. Prior administration of mepyramine had an antagonistic effect, and it is suggested that the change in tidal air is essentially the result of bronchial spasm.

Extracellular enzymes of Micropolyspora faeni found in moldy hay

“…However, the precipitins are chiefly against enzymes with chymotrypsin-like activity. We were able to demonstrate a similar 7 reaction in cattle (16). This immunological reaction against metabolic products of M. faeni was later reaffirmed by Fletcher et al (6) and then by Edwards (5).…”

“…3, 5, and 6) possess only two bands with strong enzymatic activity and, like sample 2, are towards the anode. Good hay sample 7 shows one band with chymotrypsic activity but only weakly stained; the other good hay sample (extract 8) does not show this band. For comparison we present the patterns of chymotrypsic activity in the metabolic products of M. faeni on a synthetic medium and in experimental hay culture.…”

“…Or these may be a pharmacological activity on the mucous membranes of the bronchi resulting in broncho-constriction and a decrease in tidal air. This has been observed in dogs and cats after experimental inhalation of chymotrypsin, trypsin, and other proteases (7,24). Further investigations are urgently needed to determine the exact pharmacological or enzymatic role played by these exogenous enzymes on the respiratory tract and to determine their behavior against enzyme inhibitors of the host.…”

“…We selected six samples of moldy hay from six different farms in four endemic areas where the occurrence of extrinsic allergic alveolitis in man (samples 3, 4, and 6) or in cattle (samples 1, 2, and 5) has been observed. By way of comparison, we examined two samples of good hay, one with the macroscopic appearance of good quality from a farm in an endemic area but without any history of extrinsic allergic alveolitis (sample 7), and the other from a nonendemic area (sample 8).…”