Mechanisms of the Oxytocie Activity of Papaya Proteinases

Crude papaya latex (CPL) and its proteinases, papain (PPN) and chymopapain (CPN). are strong uterine eontractants. The current study was carried out to examine possible mechanisms of the uterine stimulating activity of the proteinases. Inaetivation of the enzymatic activity of papaya proteinases reversibly abolished their uterinestimulating effect, suggesting that enzymatic activity of the proteinases is a prerequisite for their oxytocie activity. Moreover, removal of Ca""̂ from the uterine bathing medium reversibly abolished the uterine-stimulating effect of the proteinases. Nifedipine and verapamil (Ca"̂ "̂ channel bloekers) significantly and reversibly block CPL-. CPN-, and PPN-induced uterine contractions. Blockade of 5-hydroxytryptamine receptors did not prevent the oxytoeie activity of papaya proteinases. However, uterine contractions induced by the proteinases were significantly and reversibly inhibited by meelofenamie acid (a eyclooxygenase and prostaglandin inhibitor). At 0.3 and 1 mg/ml. CPL, CPN, and PPN caused a concentration-dependent increase in prostaglandin F2a production in cultured rat uterus, but only CPL (1 mg/ml) induced PGF2, production by the cultured rat uterine tissues was statistically significant. The results of the current study suggest that prostaglandin release by Ca""̂ mobilizationand proteolysis-dependent activity of papaya latex and its proteinases could play a major role in their oxytocie activity.