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 microM) resulted in a concentration-dependent formation of both dopamine and DOPAC. 3. The addition of M&B 22,948 (10 microM) 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 microM) 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 22,948 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 microM) and 8-bromo cyclic GMP (250 microM) 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.
Soares-da-Silva
P
P
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Fernandes
M H
MH
D000818:Animals; D006152:Cyclic GMP / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology; D011688:Purinones / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D011688:Purinones; C016276:8-bromocyclic GMP; D007980:Levodopa; C011145:zaprinast; D006152:Cyclic GMP; D004298:Dopamine