Guanine nucleotide- and GTP-dependent N 6-phenylisopropyladenosine stimulation of the membrane-bound cyclic AMP high affinity phosphodiesterase in rat brain

Abstract

In brain cortex, low concentrations of GTP or Gpp(NH)p activated the membrane-bound low K m cyclic AMP phosphodiesterase while higher concentrations of GTP, but not of Gpp(NH)p, reversed this activation. The adenosine analog N 6-phenylisopropyladenosine ( N 6-PIA) elicited biphasic effect on this enzyme (activation up to 10 −8 M, complete reversion at 10 −5 M), provided that GTP was present. N 6-PIA activation was reduced in the presence of Gpp(NH)p and blocked by sodium (80 mM). In contrast, the soluble low K m cyclic AMP phosphodiesterase was insensitive to GTP or N 6-PIA. This study suggests that guanine nucleotides and N 6-PIA exert their effects on the membrane-bound enzyme through guanine nucleotide regulatory proteins.