Functional characteristics of H+ -dependent nicotinate transport in primary cultures of astrocytes from rat cerebral cortex.

Article Details

Citation

Shimada A, Nakagawa Y, Morishige H, Yamamoto A, Fujita T

Functional characteristics of H+ -dependent nicotinate transport in primary cultures of astrocytes from rat cerebral cortex.

Neurosci Lett. 2006 Jan 16;392(3):207-12. Epub 2005 Oct 5.

PubMed ID
16213084 [ View in PubMed
]
Abstract

In the present study, we report the characteristics of H(+)-coupled nicotinate transport in primary cultures of astrocytes from rat cerebral cortex. The [(3)H]nicotinate transport in rat astrocytes increased up to a pH 5.5. The nicotinic acid uptake at pH 6.0 was both energy-dependent and saturable with a Michaelis constant (K(t)) of 2.8+/-0.4 mM and the maximal uptake rate (V(max)) of 31+/-3.2 nmol/mg protein/10 min. This process was reduced by a protonophore, carbonylcyanide p-trifluoromethoxyphenylhydrazone, and a typical monocarboxylate transporter (MCT) inhibitor, alpha-cyano-4-hydroxycinnamic acid, suggesting that nicotinate uptake by rat astrocytes is mediated by H(+)-coupled monocarboxylate transport system. [(3)H]Nicotinate transport in rat astrocytes was significantly inhibited by various monocarboxylic acids such as l-lactic acid and pyruvic acid with a relatively low affinity (K(i)>10 mM). On the other hand, the uptake process of l-lactic acid was also saturable with a high-affinity component (K(t)=0.27 mM) and a low-affinity component (K(t)=35.9 mM). Reverse transcription-PCR and Western blot analyses revealed that three MCT subtypes, MCT1/Slc16a1, MCT2/Slc16a7, and MCT4/Slc16a3, were expressed in these cells. Because l-lactate reduced to 67% of the nicotinate uptake even at 10mM, it is unlikely that nicotinate uptake in rat astrocytes is mediated by MCT1 and/or MCT2. These results provide biochemical evidence of a H(+)-coupled and saturable transport system, presumed to be a low-affinity monocarboxylate transporter MCT4 or other unknown H(+)-coupled monocarboxylate transport system, for nicotinate in rat cerebrocortical astrocytes.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Pyruvic acidMonocarboxylate transporter 1ProteinHumans
Unknown
Not AvailableDetails
Pyruvic acidMonocarboxylate transporter 4ProteinHumans
Unknown
Not AvailableDetails
Pyruvic acidMonocarboxylate transporter 5ProteinHumans
Unknown
Not AvailableDetails
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
NiacinMonocarboxylate transporter 4ProteinHumans
Unknown
Not AvailableDetails