A carrier relevant to human pathophysiology, drug discovery and diagnosis

In the February 2019 issue of SLAS Discovery, a study by researchers at the University of Calabria (Italy) explores the OCTNs, a small but intriguing group of carriers that opens new frontiers in drug design research to improve drug delivery and to predict drug interactions.

OCTNs mediate the flow of physiological organic cations through the plasma membrane of cells. Of the three members of the subfamily, OCTN1 and 2 are present in humans, while the OCTN3 has been lost during the course of evolution. OCTN2 plays a well-established role in maintaining homeostasis of carnitine, an essential cofactor for energy production from fatty acid metabolism. Some hereditary abnormalities of OCTN2 are at the origin of the primary deficiency of carnitine, a serious muscle pathology that can be relieved by the administration of carnitine as a drug. Remarkable deficiencies mimicking the characteristics of the disease may be caused by adverse effects caused by certain drugs interfering with the absorption of carnitine or by a strict vegetarian diet during pregnancy or childhood.

The pathophysiological role of OCTN2 is also confirmed by its presence in exosomes, nanovesicles released in the extracellular environment involved in cell-to-cell communication. Interestingly, the OCTN1 function remains relatively obscure. In fact, the removal of its gene apparently poses no problem in animals. However, some mutations of OCTN1 in humans are badociated with inflammatory diseases such as Crohn's disease.

Studies on the most recent methodological approaches highlight a link between OCTN1 and inflammation, suggesting that molecules with anti-inflammatory or antioxidant properties could be ligands of OCTN1 In this setting, ergothioneine , a mushroom metabolite and acetylcholine have been proposed. The latter is a well-known neurotransmitter that also plays a role in inflammation via a non-neuronal cholinergic system. OCTN1 and OCTN2 both have a secondary function in interaction with cationic drugs. These new discoveries open new frontiers in drug design research to improve drug delivery and predict drug interactions.

Explore further:
Discovering factors at the heart of muscular weakness

More information:
Lorena Pochini et al, OCTN: a small subfamily of carriers particularly useful for human pathophysiology, drug discovery and diagnostics, SLAS DISCOVERY: Advancing R & D in the field of life sciences (2018). DOI: 10.1177 / 2472555218812821