The antiemetic activity, gastric motor activity, and dopamine receptor effects of metoclopramide, dazopride, and sulpiride were assessed to establish if enhancement of gastric motility or antagonism of central dopamine receptors is the predominant action for drug-induced suppression of cisplatin-induced emesis. Emesis produced in dogs by cisplatin is antagonized by metoclopramide and dazopride. The antiemetic actions of metoclopramide and dazopride are associated with their ability to enhance gastric motor activity. Dazopride, unlike metoclopramide, has minimal dopamine receptor antagonist properties. Sulpiride is a potent dopamine receptor antagonist; however, it had no effect on the stomach and was ineffective in suppressing cisplatin-induced emesis.
It was suggested some years ago that the plant growth hormone, IAA4 arises from TTP through a series of reactions involving IPvA or TNH2 and IAc (13,21). Subsequently, -hen IAN was isolated from natural sources, it was proposed that IAN and IAM (14) were likely intermediates in the conversion of TTP to IAA (11). This latter view received additional support with the demonstration that IAN can be converted to IAX (19 (17). Approximately 7 to 10 days after hand pollination, when the melons were approximately 3 cm long, the outer covering (rind) was removed, and the remaining tissue sliced into thin sections. These sections were randomized and slices equivalent to two melons (10 to 12 gm) were added to a 125-ml Erlenmeyer flask containing 9 ml of M/15 KH2PO4 Each ml of buffer contained 300 units of penicillin G and 5 mg of DL-TTP (specific activity equal to 1,032,000 cpm/mg). The medium was made 1 x 103 M with respect to ascorbic acid to inhibit the destruction of IAA (2, 23). The final pH was 4.5 + 0.1. The optimum pH for the conversion of TTP to IAA by spinach tissues (25) has been reported to be 7.5, but it is also at this pH that I&A is most rapidly destroyed (20). It was deci(le(l therefore to use pH 4.5 to retard this enzymatic destruction, and even though the amouints of TTP converted woould probably be decreased, the radioactive label woould enable detection of the indole dlerivatives. In addition, the acidl pll would(l iscourage bacterial growth and enhance the stability of IPvA (1). The flasks were plugged with cotton, wrapped in black, light-proof paper and placed on a shaker at room temperature (25 ± 2°C) for 20 hours.In more receint experiments, wlhere TTP-2-C14 was incubatedI with Avena coleoptile tissue for 20 hoturs, compouin(ds apparently identical to those found in watermelon were observed. Further experiments with acetone clried powder of Avena showed these same compounds to be formed after a 30-minuite incubation periodI (unpublished, Dannenburg and Liverman). It appears then that the conversion of TTP to I&A in these experiments with watermelon tissue constitutes a normal biochemical conversion. After incubation, the flasks were placed in boiling water for 10 minutes andl then cooled. The contents and wash water from each flask were placed in a mortar and triturated with washed, ignited sand. The resulting brei was centrifuged, the supernatant was decanted,
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