Studies on the nature of the antagonistic actions of dopamine and 5-hydroxytryptamine in renal tissues.
The present work examines the possibility of whether the reciprocal effects of dopamine (DA) and 5-hydroxytryptamine (5-HT) are only dependent on the antagonistic nature of the signal resulting from the activation of their specific receptors or may also result from a competitive type of inhibition at different levels of the synthetic and metabolic pathways shared by DA and 5-HT. Studies performed in isolated proximal convoluted tubules (PCT) have shown that L-5-HTP and L-DOPA use the same transporter in order to be taken up into the cell and both L-DOPA and L-5-HTP exert a competitive type of inhibition upon their cellular uptake. The decrease in the formation of 5-HT in isolated PCT induced by L-DOPA reflects most probably a reduction in the intracellular availability of L-5-HTP. However, in experiments conducted in homogenates of PCT L-DOPA was found to be a better substrate for AAAD than L-5-HTP. Apart from sharing a common synthetic pathway, DA and 5-HT also share a common metabolic pathway; type A monoamine oxidase (MAO-A), the predominant form of MAO in rat renal tissues, converts DA into 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-HT into 5-hydroxyindolacetic acid (5-HIAA). However, in contrast to 5-HT, DA can be metabolized by MAO-B and catechol-O-methyltransferase. Inhibition of MAO-A was found to produce a 2-fold increase in the urinary excretion of 5-HT; this increase in the urinary excretion of 5-HT was accompanied by an unexpected reduction in the urinary excretion of DA.(ABSTRACT TRUNCATED AT 250 WORDS)
Institute of Pharmacology & Therapeutics, Faculty of Medicine, Porto, Portugal.
P
P
Soares-da-Silva
M A
MA
Vieira-Coelho
P C
PC
Pinto-do-O
M
M
Pestana
A M
AM
Bertorello
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D015259:Dopamine Agents / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007980:Levodopa / Q000378:metabolism; D009318:Natriuresis / Q000502:physiology; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
D015259:Dopamine Agents; D012701:Serotonin; D007980:Levodopa; D006916:5-Hydroxytryptophan; D004298:Dopamine