Actin cytoskeleton, tubular sodium and the renal synthesis of dopamine.
The present study has examined the effect of colchicine and cytochalasin B, two cytoskeleton disrupter compounds, on the formation of dopamine in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA); the deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) was also examined. The accumulation of newly formed dopamine and DOPAC in kidney slices loaded with L-DOPA (10-100 microM) was found to be dependent on the concentration of L-DOPA, being similar in control conditions and in preparations treated with increasing concentrations of colchicine (5, 10 and 50 microM). By contrast, cytochalasin B (5, 10 and 50 microM) was found to produce a concentration-dependent reduction in the formation of dopamine and of its deaminated metabolite DOPAC in kidney slices loaded with L-DOPA (10-100 microM). The inhibitory effect of cytochalasin B on the formation of dopamine was found to be completely abolished in kidney slices pretreated with ouabain (500 microM) or when sodium concentration in the incubation was reduced from 120 to 20 mM. On its own, ouabain (500 microM) was found to reduce the formation of dopamine by 55%; the effect of reducing sodium concentration in the incubation medium to 20 mM was also a significant reduction (53% decrease) in the formation of dopamine. The accumulation of DOPAC did always parallel that of its parent amine. It is concluded that the renal formation of dopamine is dependent on the concentration of sodium in the medium and the integrity of the tubular transport of sodium, namely on the association between actin cytoskeleton and Na+,K(+)-ATPase, appears to be determinant.
Soares-da-Silva
P
P
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000199:Actins / Q000037:antagonists & inhibitors*; D000818:Animals; D001692:Biological Transport; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism* / Q000502:physiology
D000199:Actins; D015102:3,4-Dihydroxyphenylacetic Acid; D003571:Cytochalasin B; D007980:Levodopa; D010042:Ouabain; D012964:Sodium; D003078:Colchicine; D004298:Dopamine