Mancha, 7307 1 Ciudad Real (M. J.Z.), Spain Within 60 min of the administration of serotonin to fasted-refed rats, there was a 5, 1 6 , and 20-fold stimulation of the mRNA coding for the cytosolic form of P-enolpyruvate carboxykinase in the kidney, small intestine and liver, respectively. This stimulation was 5, 1.3-, and 2-fold higher than noted in the same tissue after 24 h of starvation. Dose-and time-response curves to serotonin in the three tissues were similar. The level of PEPCK mRNA in the liver was significantly elevated within 30 min of serotonin administration, whereas 60 min was required in the small intestine and the kidney. The direct effect of serotonin on PEPCK mRNA was also assessed in hepatocytes maintained in primary culture. Serotonin (10-8M to 10a4M) caused a dose-dependent increase in the level of PEPCK mRNA and a transient increase in cAMP concentration. Within the first rnin of serotonin (1 O-'M) addition to cells, cAMP concentration increased 4-fold and returned after 10 min to basal level. Therefore, these results provide functional evidence of serotonin action in the rat peripheric tissues and suggest that cAMP is involved in its intracellular signalling.