Crossed desensitization between plasma kallikrein and trypsin

Area of Science:

• Pharmacology
• Physiology
• Biochemistry

Background:

• Rat uterus smooth muscle responds to enzymatic stimulation.
• Repeated exposure to enzymes can lead to desensitization.
• The specific mechanisms underlying enzyme-induced uterine desensitization require further investigation.

Purpose of the Study:

• To investigate the phenomenon of desensitization in rat uterus smooth muscle upon repeated exposure to specific enzymes.
• To explore the cross-reactivity of desensitization between different enzymes (kallikrein, trypsin, chymotrypsin).
• To elucidate the potential involvement of endogenous inhibitors in enzyme-induced desensitization.

Main Methods:

• Isolated rat uterus preparations were utilized.
• Enzymes including rat plasma kallikrein, trypsin, and chymotrypsin were added cumulatively to the organ bath.
• Contraction responses were measured and analyzed to assess desensitization and cross-reactivity.

Main Results:

• Rat plasma kallikrein and trypsin induced uterine contractions, with desensitization occurring after repeated additions.
• Higher enzyme doses could overcome desensitization.
• Desensitization to kallikrein did not affect trypsin response, but trypsin desensitization impaired kallikrein response.
• Chymotrypsin, while not causing contraction, induced insensitivity to both kallikrein and trypsin, suggesting inhibitor release.

Conclusions:

• Rat uterus smooth muscle exhibits enzyme-specific desensitization.
• The findings suggest the potential release of endogenous inhibitors, possibly specific to kallikrein and trypsin, contributing to desensitization.
• Bradykinin is unlikely to be involved in the contraction mechanism.
• Chymotrypsin's effect may also be mediated by the release of similar inhibitory substances.