MRP5 Activators

MRP5 activators, as described in the table above, primarily focus on modulating intracellular levels of cAMP, a known substrate of MRP5. This approach indirectly enhances MRP5 activity, given the transporter's role in cellular efflux of cAMP. Forskolin, Prostaglandin E2, Dibutyryl-cAMP, and Rolipram are notable in this regard, as they directly or indirectly increase cAMP levels. Forskolin, for instance, activates adenylate cyclase, leading to elevated cAMP levels. Prostaglandin E2 exerts similar effects through its receptors. Dibutyryl-cAMP, being a cAMP analog, mimics the action of cAMP, potentially enhancing MRP5-mediated transport. Rolipram, as a phosphodiesterase inhibitor, prevents cAMP degradation, indirectly increasing its availability for MRP5 transport.

In addition to cAMP modulation, some chemicals in this list, such as Vinblastine and Verapamil, are recognized for their roles in modulating MRP1, a closely related ABC transporter. Their effects on MRP5, however, are more speculative and may involve complex interactions within the cellular environment. Sulindac, Epinephrine, IBMX, Curcumin, Caffeine, and Theophylline represent a diverse range of chemicals, each influencing cAMP levels through various mechanisms. Sulindac, as a nonsteroidal anti-inflammatory drug, may alter cAMP levels, affecting MRP5 indirectly. Epinephrine, through adrenergic receptors, and IBMX, as a non-specific phosphodiesterase inhibitor, elevate cAMP levels, which could enhance MRP5 function. Curcumin's multifaceted role in cellular signaling pathways suggests potential indirect effects on MRP5. Caffeine and Theophylline, similar to Rolipram, inhibit phosphodiesterase and thus may increase cAMP levels, indirectly affecting MRP5 activity.