Guanine nucleotide‐ and GTP‐dependent N6‐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.