Inhibitory effects of guanosine 3′: 5′‐cyclic monophosphate on the synthesis of dopamine in the rat kidney

1 In the present study the effects of M&B 22,948, a guanosine 3′: 5′‐cyclic monophosphate (cyclic GMP) selective phosphodiesterase inhibitor and of 8‐bromo cyclic GMP were examined on the synthesis of dopamine from l ‐3,4‐dihydroxyphenylalanine ( l ‐DOPA) in rat cortical slices and in whole kidney homogenates. The deamination of newly‐formed dopamine into 3,4‐dihydroxyphenylacetic acid (DOPAC) was also studied. The assay of l ‐DOPA, dopamine, noradrenaline and DOPAC was performed by high performance liquid chromatography (h.p.l.c.) with electrochemical detection. 2 Incubation of renal slices and homogenates of whole kidney with exogenous l ‐DOPA (0.1–10.0 μ m ) resulted in a concentration‐dependent formation of both dopamine and DOPAC. 3 The addition of M&B 22,948 (10 μ m ) to the incubation medium resulted in a marked reduction in the accumulation of both newly‐formed dopamine and DOPAC in kidney slices; the inhibitory effect of M&B 22,948 on DOPAC formation was greater than that on dopamine. 8‐Bromo cyclic GMP (250 μ m ) produced only a slight decrease in the tissue levels of newly‐formed dopamine (5–13% reduction), but was found to decrease significantly (51–68% reduction) the formation of DOPAC in kidney slices. The addition of 8‐bromo cyclic GMP plus M&B 22,498 to the incubation medium resulted in similar effects to those described for M&B 22,948 alone. 4 In kidney homogenates, in contrast to results observed in kidney slices, M&B 22,948 (10 μ m ) and 8‐bromo cyclic GMP (250 μ m ) were found to affect neither the formation of dopamine nor its deamination to DOPAC. 5 In conclusion, the results presented here suggest that cyclic GMP may be involved in the regulation of dopamine synthesis, probably through the control of the entry of l ‐DOPA into the tubular epithelial cells.