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

Open Access
Publisher Website
Google Scholar
Abstract
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 μm) resulted in a concentration-dependent formation of both dopamine and DOPAC. 3 The addition of M&B 22,948 (10 μm) 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 μm) 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 μm) and 8-bromo cyclic GMP (250 μm) 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.