SEEING THROUGH A GLASS DARKLY - CASTING LIGHT ON IMIDAZOLINE I-SITES

Although imidazoline sites have been the subject of research for sever al years, there is still controversy about their structure, diversity and physiology. The I-1 site is thought to exist principally as a bind ing site and is widely purported to play a role in controlling systemi c blood pressure, although this is still unclear. The majority of I-2 sites are widely accepted as being allosteric sites on monoamine oxida se; however, even with selective ligands, their exact function remains to be determined. A putative I-3 site modulates insulin secretion and could represent the first functional site to be pharmacologically def ined with selective agonists and antagonists. The structure and releva nce of the proposed endogenous ligand 'clonidine-displacing substance' remains elusive. A potential candidate for this substance is agmatine ; however, although it is capable of displacing bound clonidine from i midazoline sites, it lacks the functionality ascribed to the clonidine -displacing substance. In this review, Richard M. Eglen and colleagues assess our knowledge of imidazoline sites in the light of recent data .