Stereospecificity in binding studies. A useful criterion though insufficient to prove the presence of receptors.
In binding studies, stereospecificity is not a property restricted to receptor sites; indeed stereospecific binding has also been observed for acceptor sites. Therefore it does not represent a decisive criterion to make a binding site, a receptor site. However, in some well established cases, it can be useful especially when the difference between the active and inactive enantiomer exceeds 1000-fold as is the case for dexetimide and levetimide on muscarinic receptors. Stereospecific effect is also detectable with acceptor sites, e.g. spirodecanone sites, levocabastine displaceable neurotensin and, presumably, many other ones. Since the membrane is chiral (L-aminoacid) one should expect that non-specific displaceable binding would also display stereospecificity. In this regard, as most of the Scatchard plots reported throughout the literature are curvilinear, even if a straight line is drawn, one may assume that this is due to the presence of acceptor sites that are labelled by the ligand in addition to receptor sites. One cannot exclude the repetition of another "levocabastine story" with other neuropeptides. Hence, as the biochemical criteria like high affinity, saturability, reversibility and stereospecificity cannot differentiate a receptor from an acceptor (see Table 1), the most important and decisive criteria remain: (1) the drug displacement with compounds belonging to different pharmacological classes but mostly to different chemical classes, and (2) the functional correlates between the binding affinity and the potency in pharmacological or physiological tests in vitro or in vivo. When these points are fulfilled a binding site may be called a receptor site.
Laduron
P M
PM
Centre de Recherches, Rhône-Poulenc Santé, Vitry-sur Seine, France.
D000818:Animals; D008968:Molecular Conformation; D009496:Neurotensin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D013141:Spiro Compounds / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D011956:Receptors, Cell Surface; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D013141:Spiro Compounds; C014826:spirodecanone; D009496:Neurotensin