Opposite effects of WR-2721 and WR-1065 on radiation-induced hypothermia: possible correlation with oxygen uptake.
Ionizing radiation induces hypothermia in guinea pigs. While systemic injection of the radioprotectant S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) did not block hyperthermia induced by exposure to 10 Gy of gamma radiation, central administration did attenuate it. The dephosphorylated metabolite of WR-2721, N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065), accentuated radiation-induced hypothermia by both routes of administration. In brain homogenates, oxygen uptake was inhibited by WR-2721 but elevated by WR-1065. These results suggest that the antagonism of radiation-induced hypothermia found only after central administration of WR-2721 is due to its direct actions and not to its dephosphorylated metabolite and that this effect may be correlated with the inhibition by WR-2721 of oxygen uptake.
Kandasamy
S B
SB
Behavioral Sciences Department, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20814-5145.
Kumar
K S
KS
Hunt
W A
WA
Weiss
J F
JF
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000378:metabolism; D003037:Cobalt Radioisotopes; D005720:Gamma Rays; D006168:Guinea Pigs; D007035:Hypothermia / Q000517:prevention & control*; D008297:Male; D008624:Mercaptoethylamines / Q000627:therapeutic use*; D009946:Organothiophosphorus Compounds / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*
D003037:Cobalt Radioisotopes; D008624:Mercaptoethylamines; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D004999:Amifostine