Mechanism of Inactivation of Oxytocin by Rat Kidney Enzymes

Of 10 different rat tissues examined, only homogenates of kidney, spleen and liver rapidly inactivated crystalline deaminodicarba-oxytocin—a biologically active analog of oxytocin which is resistant to aminopeptidases and redox reactions involving the disulfide bond of neurohypophyseal hormones. Kidney homogenate showed the highest degree of inactivating activity, and essentially all the enzymic activity was recovered in the centrifugal supernatant; this finding supports the contention that the kidney is the major organ involved in the inactivation of oxytocin. A partially purified enzyme preparation obtained from this soluble protein fraction inactivated oxytocin, deaminodicarba-oxytocin, [8-phenylalanine]-oxytocin, bradykinin and angiotensinamide. The enzyme preparation did not inactivate a series of neurohypophyseal peptide analogs in which the leucine residue in position 8 of oxytocin is replaced by glutamine, serine, valine or alanine, nor did it inactivate [8-arginine]-vasopressin. Product identification revealed that oxytocin, deamino-dicarba- oxytocin and [8-phenylalanine]-oxytocin were initially attacked at the peptide linkage between the leucine and glycine residues, resulting in the release of glycinamide. (Endocrinology88: 633, 1971)