Autoregulation of H⁺/lactate efflux prevents monocarboxylate transport (MCT) inhibitors from reducing glycolytic lactic acid production.

ABSTRACT:

Background

Pharmacological inhibition of membrane transporters is expected to reduce the flow of solutes, unless flux is restored (i.e., autoregulated) through a compensatory increase in the transmembrane driving force. Drugs acting on monocarboxylate transporters (MCTs) have been developed to disrupt glycolytic metabolism, but autoregulation would render such interventions ineffective. We evaluated whether small-molecule MCT inhibitors reduce cellular H⁺/lactate production.

Methods

Cellular assays measured the relationship between MCT activity (expressed as membrane H⁺/lactate permeability; P_HLac) and lactic acid production (inferred from H⁺ and lactate excretion; J_HLac) in a panel of pancreatic ductal adenocarcinoma (P

SUBMITTER: Blaszczak W 

PROVIDER: S-EPMC9519749 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature