INHIBITORY EFFECTS OF GUANOSINE 3'-5'-CYCLIC MONOPHOSPHATE ON THE SYNTHESIS OF DOPAMINE IN THE RAT-KIDNEY

• Type: Article in International Scientific Journal
• Date: 1991

Authors

soares-da-silva, p (Author) FMUP; Fernandes MH (Author) FMDUP

Journal

Title: British Journal of Pharmacology

Vol. 103

Pages: 1923-1927

ISSN: 0007-1188

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 20 Citations

Scopus - 18 Citations

Other information

Authenticus ID: P-001-QHX

DOI: 10.1111/j.1476-5381.1991.tb12353.x

Abstract (EN): 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-mu-M) resulted in a concentration-dependent formation of both dopamine and DOPAC. 3 The addition of M&B 22,948 (10-mu-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-mu-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-mu-M) and 8-bromo cyclic GMP (250-mu-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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5