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

• Type: Article in International Scientific Journal
• Date: 2001

Authors

Benedita Sampaio-Maia (Author) Other; Serrão, MP (Author) Other; Soares-da-Silva, P (Author) Other

Journal

Title: American Journal of Physiology - Cell Physiology

Vol. 280 No. 2

Pages: C333-C342

ISSN: 0363-6143

Publisher: American Physiological Society

Other information

Authenticus ID: P-010-DXV

DOI: 10.1152/ajpcell.2001.280.2.c333

Abstract (EN): <jats:p>We examined the nature and regulation of the inwardl-3,4-dihydroxyphenylalanine (l-DOPA) transporter in rat capillary cerebral endothelial (RBE4) cells, type 1 astrocytes (DI TNC<jats:sub>1</jats:sub>), 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 TNC<jats:sub>1</jats:sub>cells was the effect of maneuvers that increase intracellular cAMP levels accompanied by increases inl-DOPA uptake. Also, only in DI TNC<jats:sub>1</jats:sub>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 inl-DOPA accumulation. In all three cell types, the Ca<jats:sup>2+</jats:sup>/calmodulin inhibitors calmidazolium and trifluoperazine inhibited l-DOPA uptake in a noncompetitive manner. Thapsigargin (1 and 3 ¿M) and A-23187 (1 and 3 ¿M) failed to alter l-DOPA accumulation in RBE4 and Neuro-2a cells but markedly increased l-DOPA uptake in DI TNC<jats:sub>1</jats:sub>cells. We concluded that l-DOPA in RBE4, DI TNC<jats:sub>1</jats:sub>, and Neuro-2a cells is transported through the L-type amino acid transporter and appears to be under the control of Ca<jats:sup>2+</jats:sup>/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 Ca<jats:sup>2+</jats:sup>and cAMP and to decreases in cGMP.</jats:p>

Language: English

Type (Professor's evaluation): Scientific