Difference in behaviour between synthetic and endogenous substance P in human plasma.

Abstract

While endogenous immunoreactive substance P (SP) is relatively stable in human plasma in vitro and gives the same radioimmunoassay results after several weeks of cold storage, added synthetic exogenous substance P can be only partially recovered from fresh plasma and disappears from it rapidly. The recovery of added SP can be improved by heatinactivation of the plasma before addition of SP, but the rate of disapparance of exogenous SP from plasma, though slower, cannot be fully prevented. When SP is added to plasma before heat-inactivation the recovery becomes unexpectedly low. When teprotide (SQ 20881), a specific inhibitor of the angiotensin converting enzyme in vivo, is added to fresh plasma, it causes an apparent increase in endogenous immunoreactive SP, proportional to the concentration of teprotide used. Teprotide, added to plasma containing synthetic SP, partially prevents the rapid loss of SP-like immunoreactivity. Of other enzyme inhibitors tested, 1,10-phenanthroline causes an apparent increase in endogenous immunoreactive SP, and ethylenediamine tetraacetic acid (EDTA) an apparent increase in recovered exogenous SP. Charcoal extraction studies show that while exogenous SP is fully adsorbed, endogenous SP is not. A possible explanation for the different behaviour of synthetic SP and endogenous plasma SP could be that endogenous SP may exist in plasma in a high molecular weight form or attached to a carrier protein.