Uroporphyria development in cultured chick embryo fibroblasts long-term treated with chloramphenicol and ethidium bromide

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.