Prostaglandin transport

Abstract

Newly synthesized prostaglandins (PGs) efflux from cells by simple diffusion, driven by pH and the membrane potential. Metabolic clearance requires energy-dependent uptake across the plasma membrane, followed by cytoplasmic oxidation. Several PG carriers have been cloned and characterized. PGT is broadly expressed in cyclooxygenase (COX)-positive cells, appears to be a lactate/PG exchanger, and is coordinately regulated with COX. By analogy with neurotransmitter release and re-uptake, PGT may regulate pericellular PG levels via re-uptake. PGT may also direct PGs towards and/or away from specific sets of PG receptors. Other members of the OATP transporter family also catalyze PG uptake; these are variably expressed and have variable affinities for PGs. The OATs are alpha-ketoglutarate/organic anion exchangers that accept PGs; these probably represent the uptake step in renal and hepatic PG degradation and excretion. Finally, certain glutathione-conjugated leukotrienes and PGs are actively extruded from cells by the MRPs; these may also play a role in metabolic clearance of PGs.