Effect of probenecid, verapamil and progesterone on the concentration-dependent and temperature-sensitive human erythrocyte uptake and export of guanosine 3′,5′ cyclic monophosphate (cGMP)

Abstract

Elevated extracellular cGMP levels have been observed in various clinical conditions, and the analyte has been proposed as a diagnostic marker of cardiovascular as well as malignant diseases. However, the use of extracellular cGMP as a pathophysiological marker requires detailed knowledge about the cellular bio-kinetics of cGMP (synthesis, metabolic conversion and export). In the present study the transport of cGMP in human erythrocytes has been further characterized. The uptake of cGMP was dependent on a concentration gradient and was temperature-sensitive, compatible with passive diffusion. The cGMP export was temperature-sensitive, saturable (K_m = 3.4 ± 1.0 μmol 1⁻¹), inhibited by probenecid and verapamil and stimulated by progesterone. The results show that human erythrocytes possess a cGMP transport system similar to that found in other cells and that extracellular levels of cGMP are dependent on intracellular levels, membrane transport and influenced by physiological factors and pharmacological agents.

Key Words:

• cellular transport
• cGMP
• pharmacology
• physiology
• tumor marker