Study give insight into how drugs get inside its target

Researchers in the UK have discovered how drugs that have been used to kill the parasite that causes sleeping sickness actually work, a finding that can potentially impact our understanding of drug distribution in many different diseases.
Research has revealed that the drugs used to attack Trypanosoma brucei enter through pores in the parasite's cells known as aquaporins which function as water channels.
It is the first time that drugs have been shown to enter cells through aquaporins and this may have major implications for drug delivery in other diseases.
Dr Harry de Koning, a Reader of Biochemical Parasitology at the University of Glasgow who has been studying drug resistance mechanisms in pathogenic protozoan parasites, said:

This research is a breakthrough in understanding how the drugs used to attack the sleeping sickness parasite get inside their target: like spies into an enemy castle they enter through a water channel.
The discovery heralds a new paradigm for drug uptake by cells, as this is the first time that drugs have been shown to enter cells through aquaporins.

Although there have been some reports of these channels being permeable to inorganic ions or small molecules, this is the first detailed report of an aquaporin acting as a genuine transport protein rather than a passive channel for mainly water.

The Glasgow researchers, in collaboration with Professor David Horn of the University of Dundee, identified a genetic link between a single parasite gene and its susceptibility to the drugs pentamidine and melarsoprol, which were first introduced in the 1930s and 1940, respectively.
The gene in question coded for one of the trypanosome s channels for water and glycerol, aquaporin 2 (TbAQP2).
Aquaporins are found in virtually all organisms, from bacteria to humans, selectively mediating the uptake or release of water and/or glycerol, thus maintaining osmotic equilibrium.
At least thirteen different aquaporins are expressed in various human tissues, and hundreds of others have been identified in other species, comprising a large and highly conserved gene family.

Their vital importance to life was recognised with a Nobel Prize, in 2003, to the discoverer of the first aquaporin gene.
Dr De Koning said, "Although the phenomenon of melarsoprol/pentamidine cross-resistance was first described in 1951 it had never been satisfactorily explained."
The current study, published in the Journal of Antimicrobial Chemotherapy, by identifying and characterising the melarsoprol/pentamidine transporter, finally resolves this vital issue.
As virtually all living cells express aquaporins, this discovery has potentially far-reaching implications for cellular transport and permeation mechanisms, potentially impacting on our understanding of drug distribution in many different diseases.
The research was funded by the Medical Research Council and The Wellcome Trust, the Glasgow University said in a release.