The disappearance of phe(3)-oxytocin, val(3)-oxytocin and oxytocin from the circulation of male rats was shown to be due to qualitatively similar mechanisms, that is, it depends on uptake in the kidneys and organs of the splanchnic vascular area. However, compared to phe(3)-oxytocin and oxytocin (whose half-lives were essentially similar) val(3)-oxytocin took twice as long to reach half its initial blood concentration. In lactating rats the mammary glands probably participated in the uptake of phe(3)-oxytocin, but the rate of disappearance of val(3)-oxytocin was not different from that in non-lactating animals. In male nephrectomized rats without splanchnic circulation, phe(3)-oxytocin, unlike val(3)-oxytocin, was quickly distributed in a volume equal to two-thirds of the total body water. Using oxytocin as the standard, val(3)-oxytocin and phe(3)-oxytocin were more potent when assayed on a superfused uterus or on a rat uterus in vivo than when assayed by the pharmacopoeial method (1958) on the isolated uterus in an organ bath. The difficulties of assaying oxytocin analogues against oxytocin (or the international standard preparation) are discussed.
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