Guanine nucleotide- and GTP-dependent N6-phenylisopropyladenosine stimulation of the membrane-bound cyclic AMP high affinity phosphodiesterase in rat brain.
In brain cortex, low concentrations of GTP or Gpp(NH)p activated the membrane-bound low Km cyclic AMP phosphodiesterase while higher concentrations of GTP, but not of Gpp(NH)p, reversed this activation. The adenosine analog N6-phenylisopropyladenosine (N6-PIA) elicited biphasic effect on this enzyme (activation up to 10(-8) M, complete reversion at 10(-5) M), provided that GTP was present. N6-PIA activation was reduced in the presence of Gpp(NH)p and blocked by sodium (80 mM). In contrast, the soluble low Km cyclic AMP phosphodiesterase was insensitive to GTP or N6-PIA. This study suggests that guanine nucleotides and N6-PIA exert their effects on the membrane-bound enzyme through guanine nucleotide regulatory proteins.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000494:pharmacology
D010660:Phenylisopropyladenosine; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D012964:Sodium; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000241:Adenosine