Regulatory pathways and uptake of L-DOPA by capillary cerebral endothelial cells, astrocytes, and neuronal cells

• Tipo: Artigo em Revista Científica Internacional
• Data: 2001

Autores

Benedita Sampaio-Maia (Autor) FMDUP; Paula Serrão (Autor) Outra; Soares-da-Silva P (Autor) FMDUP

Revista

Título: American Journal of Physiology - Cell Physiology

Vol. 280 Nº 2

Páginas: C333-C342

ISSN: 0363-6143

Editora: American Physiological Society

Indexação

ISI Web of Knowledge - 30 Citações

ISI Web of Science

Scopus - 36 Citações

Pubmed / Medline

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

CORDIS: Ciências da Saúde

Outras Informações

ID Authenticus: P-000-WE2

Abstract (EN): We examined the nature and regulation of the inward L-3,4-dihydroxyphenylalanine (L-DOPA) transporter in rat capillary cerebral endothelial (RBE4) cells, type 1 astrocytes (DI TNC1), and Neuro-2a neuroblastoma cells. In all three cell types, the inward transfer of L-DOPA was largely promoted through the 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid-sensitive and sodium-independent L-type amino acid transporter. Only in DI TNC1 cells was the effect of maneuvers that increase intracellular cAMP levels accompanied by increases in L-DOPA uptake. Also, only in DI TNC1 cells was the effect of the guanylyl cyclase inhibitor LY-83583 accompanied by a 65% increase in L-DOPA accumulation, whereas the nitric oxide donor sodium nitroprusside produced a 25% decrease in L-DOPA accumulation. In all three cell types, the Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L-DOPA uptake in a noncompetitive manner. Thapsigargin (1 and 3 microM) and A-23187 (1 and 3 microM) failed to alter L-DOPA accumulation in RBE4 and Neuro-2a cells but markedly increased L-DOPA uptake in DI TNC1 cells. We concluded that L-DOPA in RBE4, DI TNC1, and Neuro-2a cells is transported through the L-type amino acid transporter and appears to be under the control of Ca2+/calmodulin-mediated pathways. Astrocytes, however, are endowed with other processes that appear to regulate the accumulation of L-DOPA, responding positively to increases in intracellular Ca2+ and cAMP and to decreases in cGMP.

Idioma: Inglês

Tipo (Avaliação Docente): Científica