Understanding the Mechanism of Action of CCCP in Intestinal Brush-Border Membrane Function

The brush-border membrane (BBM) plays a crucial role in maintaining the integrity of intestinal epithelial cells by regulating the transport of ions and nutrients. One key player in this process is carbonyl cyanide-m-chlorophenylhydrazone (CCCP), a molecule that has been shown to have significant effects on the function of the BBM. But what exactly does CCCP do, and how does it interact with the intestinal epithelial cells?

Recent studies have shed light on the mechanism of action of CCCP in the context of intestinal physiology. It appears that CCCP does not primarily act by dissipating any imposed pH gradient across the BBM, as previously thought. Instead, its primary function is to directly inhibit the pH gradient-activated chloride (Cl-) uptake and Cl-/Cl-exchange activities characteristic of the BBM.

To investigate this phenomenon further, researchers used 36Cl and BBM vesicles from guinea pig ileum to quantify the effect of CCCP on Cl- uptake across the BBM. Their findings showed that CCCP partially inhibited both pH gradient-activated Cl- uptake and Cl-/Cl-exchange activities present in these vesicles.

In contrast to its effects on Cl- uptake, CCCP had no significant impact on the initial decay rate of an imposed proton gradient, as determined using the pH-sensitive fluorophore pyranine. This suggests that CCCP's mechanism of action is specific to the regulation of ion transport across the BBM and does not involve disruption of proton gradients.

In summary, the results strongly indicate that the primary action of CCCP in intestinal physiology is to inhibit directly the pH gradient-activated Cl- uptake and Cl-/Cl-exchange activities characteristic of the BBM. This understanding is crucial for further research into the regulation of ion transport across the intestinal epithelium and may have important implications for our understanding of various gastrointestinal disorders.

What is cccp