It is recommended that, before prescribing sildenafil for erectile dysfunction, clinicians should caution their patients and their partners on the possibility of neurologic, emotional, or psychological disturbances; amnesia or loss of consciousness; or aggressive behavior.

A survey was conducted of the distribution of l-asparagine synthetase and of l-asparaginase in the principal organs of representative mammals and birds. Although a radiometric assay was used as a routine, several additional criteria, including enzymic and chromatographic ones, were used to verify that the product of the synthetase was l-asparagine. Recoveries of exogenous l-asparagine were assessed in the presence of a number of mouse organs and found to be about 85%. In addition, evidence is presented for the existence in mouse liver of a thermolabile activity capable of destroying l-asparagine and stimulated by high concentrations of NH(4) (+) ions. Of the organs surveyed, pancreas was generally found to synthesize l-asparagine at the most rapid rate, whereas extracts of liver catalysed the decomposition of this amide at the greatest velocity. Of the species studied, guinea pig had the highest activities of pancreatic l-asparagine synthetase and also of hepatic l-asparaginase. The pancreas of mouse and ox also were good sources of l-asparagine synthetase.

l-Asparagine synthetase was partially purified from mouse pancreas to a final mean specific activity of 0.10 unit/mg of protein. The enzyme exhibited an l-glutaminase activity which was not affected by l-asparate, NH(4)Cl, ATP-MgCl(2), l-glutamate, AMP (sodium salt) or sodium pyrophosphate. The l-glutamine-dependent l-asparagine synthetase activity of the partially purified enzyme from mouse pancreas was markedly decreased by freezing for 7 days at -87 degrees C in the presence of 1mm-dithiothreitol, but effectively protected from inactivation by high concentrations (10mm) of the thiol reagent. The l-glutaminase activity of the enzyme was inhibited by antagonists of l-glutamine (e.g. 6-diazo-5-oxo-l-norleucine, 5-chloro-4-oxo-l-norvaline, 5-diazo-4-oxo-l-norvaline and NSC-163501) and thiol-reactive compounds (e.g. 2-amino-4-arsenophenol hydrochloride, maleimide, mucochloric acid and ZnCl(2)), but not by aminomalonic acid, the next lower homologue of l-aspartate, nor by l-homoserine beta-adenylate, an analogue of the presumed transitory covalent intermediate. The complete forward reaction catalysed by l-asparagine synthetase from mouse pancreas appears to be irreversible and essentially stoicheiometric under the conditions examined. Mouse pancreas contains a proteolytic inhibitor of l-asparagine synthetase separable from the enzyme by ion-exchange column chromatography. The inhibitor is activated by incubation at 4 degrees C for 110h and inactivated by soya-bean trypsin inhibitor, di-isopropyl phosphorofluoridate and boiling.