Effects of dimethyl sulfoxide and other dipolar aprotic solvents on rat hepatic adenylate cyclase. Potentiating effects on glucagon and guanylylimidodiphosphate stimulation.
The actions of dimethyl sulfoxide (DMSO), acetone and two other aprotic solvents on the activity of rat hepatic adenylate cyclase were studied in order to detect their possible effects on both hormonal and nonhormonal enzyme stimulation. The glucagon- or guanylylimidodiphosphate [Gpp(NH)p]-stimulated activity was significantly increased by all DMSO concentrations (0.08--2.57 M) while the highest concentrations of this solvent decreased the enzyme activity stimulated by sodium fluoride. The effect of DMSO on adneylate cyclase activity is reversible and the stimulatory effect of this drug can be seen even on adenylate cyclase activity in the persistent active state induced by preincubation of the enzyme with Gpp(NH)p. An increase in adenylate cyclase activity stimulated by glucagon or Gpp(NH)p was also seen after the addition of other aprotic solvents (acetone, acetonitrile and dimethylformamide) to the assay system. These effects of aprotic solvents on the rat hepatic adenylate cyclase activity may be caused by an increase of membrane fluidity and facilitated movement of the adenylate cyclase subunits in the plane of the cell membrane.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004357:Drug Synergism; D005934:Glucagon / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology*; D051381:Rats; D012997:Solvents / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013997:Time Factors
D012997:Solvents; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D005934:Glucagon; D000262:Adenylyl Cyclases; D004121:Dimethyl Sulfoxide