Incubation of big endothelin‐3 (big ET‐31–41) with the membrane fraction obtained from cultured endothelial cells (ECs) resulted in an increase in immunoreactive‐ET (IR‐ET). This increasing activity was markedly suppressed by phosphoramidon, which is known to inhibit the conversion of big ET‐11–39 to ET‐11–21. Reverse‐phase HPLC of the incubation mixture of the membrane fraction with big ET‐3 revealed one major IR‐ET component corresponding to the elution position of synthetic ET‐31–21. When the cultured ECs were incubated with big ET‐3, a conversion to the mature ET‐3, as well as an endogenous ET‐1 generation, was observed. Both responses were markedly suppressed by phosphoramidon. By the gel filtration of 0.5% CHAPS‐solubilized fraction of membrane pellets or ECs, the molecular mass of the proteinase which converts big ET‐1 and big ET‐3 to their mature form was estimated to be 300–350 kDa. Phosphoramidon almost completely abolished both converting activities of the proteinase. We conclude that the above type of phosphoramidon‐sensitive metalloproteinase functions as an ET‐converting enzyme to generate the mature form from big ET‐1 and big ET‐3 in ECs.

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The purpose of this study was to evaluate the bioavailability of dic10fenac sodium following stomal or rectal administration in patients after rectal surgery, and to compare it with that following rectal administration in healthy volunteers. Research into the efficacy of different routes of administration of a single dose of a nonsteroidal analgesic suppository (Voltaren® suppository) was carried out in order to investigate the degree of efficacy in patients after rectal surgery, i.e. in patients following rectal amputation (Miles group, n = 5), in patients after sphincter-and anus-preserved colorectal resection (LAR group, n = 5) and in a control group (n = 5). The Miles group demonstrated half the maximum plasma drug concentration (Cmax) and area under the plasma concentration-time curve (AUC) values found in the control group. However, the LAR group showed a plasma concentration curve similar to that of the control group. With regard to absorption of the suppository after rectal surgery, preservation of the proctal canal is a key factor in obtaining normal absorption. In the present study, none of the participating patients complained of discomfort at the application site. As one form of administration for nonsteroidal analgesics, the suppository was found to be effective and useful in patients of both the Miles and LAR groups after rectal surgery in whom oral administration was not possible.