METABOLISM OF VASOPRESSIN, OXYTOCIN AND THEIR ANALOGS [MPA(1), D-ARG(8)]-VASOPRESSIN (DDAVP) AND [MPA(1), D-TYR(ET)(2), THR(4), ORN(8)]OXYTOCIN (ANTOCIN) IN HUMAN KIDNEY AND LIVER HOMOGENATES
A. Fjellestadpaulsen et S. Lundin, METABOLISM OF VASOPRESSIN, OXYTOCIN AND THEIR ANALOGS [MPA(1), D-ARG(8)]-VASOPRESSIN (DDAVP) AND [MPA(1), D-TYR(ET)(2), THR(4), ORN(8)]OXYTOCIN (ANTOCIN) IN HUMAN KIDNEY AND LIVER HOMOGENATES, Regulatory peptides, 67(1), 1996, pp. 27-32
Information regarding the metabolic fate of the neurohypophyseal hormo
nes arginine-vasopressin (AVP), oxytocin (OT) and their analogues in m
an is practically non-existent. The aim of the present study was to in
vestigate the stability of oxytocin, vasopressin and their analogues d
DAVP and [Mpa(1)-D-Tyr(2)(Et), Thr(4), Om(8)]-oxytocin (antocin) in hu
man renal microvilli brush border membranes and in human liver membran
es. After incubation the extent of degradation of the peptides was det
ermined by reversed phase high-performance liquid chromatography (HPLC
). The degradation of both AVP and OT was rapid in the presence of glu
tathione and human renal microvilli membranes. AVP, as well as dDAVP,
was stable when incubated with microvilli membranes without glutathion
e, while OT was metabolized. The metabolization of the oxytocin analog
ue, antocin, also varied with the presence of glutathione. While in th
e absence of glutathione a more Lipophilic peak eluted, a more hydroph
ilic peak was observed with glutathione on HPLC. The lipophilic peak w
as found to coelute with the truncated analogue [Mpa(1), D-Tyr(2) (Et)
, Thr(4), desOm(8), Gly(9)]-oxytocin. No degradation occurred when the
peptides were incubated with liver membranes. However, when using cru
de, unpurified liver homogenate degradation occurred for all peptides
except antocin. The degradation of AVP in the human unpurified liver h
omogenate was as rapid as in the renal microvilli membranes. Similarly
, OT was more rapidly degraded in human kidney microvilli membranes in
the presence of glutathione than in the human crude liver homogenate,
when using equal amounts of protein in the incubations. Thus, the pre
sent investigation indicates the existence of two possible metabolic p
athways, in kidney microvilli, one for OT, which did not require the p
resence of reduced glutathione, and one for AVP, which required the pr
esence of reduced glutathione. Liver degradation, on the other hand, r
equires the hepatocytes.