US EPA

1032038 

Journal Article 

Effects of phenylarsine oxide on agonist-induced hepatic vasoconstriction and glycogenolysis 

Steinhelper, ME; Olson, MS 

1988 

Yes 

Biochemical Pharmacology
ISSN: 0006-2952
EISSN: 1873-2968 

NIOSH/00180486 

37 

6 

1167-1169 

English 

2895653 

10.1016/0006-2952(88)90526-6 

WOS:A1988M751900028 

A study was conducted to determine whether organic trivalent arsenicals exert effects on certain specific physiological and pathophysiological glycogenolytic/vasoconstrictive agonists in the perfused liver. The dose receptor relocations for phenylephrine stimulated glycogenolysis and vasoconstriction in the presence and absence of phenylarsine-oxide (637036) (PhAsO) were determined. At concentrations of phenylephrine which do not constrict the hepatic vasculature, PhAsO had very little effect on phenylephrine stimulated glycogenolysis. At concentrations of phenylephrine which increased portal vein pressure markedly, PhAsO inhibited completely the hepatic hemodynamic response to phenylephrine while inhibiting phenylephrine stimulated glycogenolysis by only 30 percent. Apparently PhAsO selectively inhibits the indirect effects of phenylephrine on mediation of vasoconstriction induced local ischemia. The effects of other hepatic agonists which likely exert their glycogenolytic effects either directly through interaction with parenchymal cells or indirectly through interaction with nonparenchymal cells were also studied. Studies were also performed of the ability of thiol compounds to reverse PhAsO inhibition of phenylephrine induced vasoconstriction and glycogenolysis. The author concludes that a major result of toxic arsenical exposure may be a diminished responsiveness of cells to various autacoid signals. Such cellular desensitization may participate in the development of the pathological lesions that characterize arsenical toxicosis. 

DCN-169030; Arsenic compounds; Arsenic poisoning; Hepatotoxicity; Vasoactive agents; Liver enzymes; Glycoproteins; Toxic effects