HETEROGENEITY IN LIGAND RECOGNITION OF CALCITONIN RECEPTORS

Comparison was made of the ligand recognition profile of calcitonin re ceptors from human, rat, pig and sheep using competition binding assay s performed under standardised conditions. Ligands representative of t he three classes of calcitonin (CT), human, pig and salmon, were used to discriminate ligand-receptor interaction in each case. Although for all receptor preparations the relative affinity for the ligands was s almon CT greater than or equal to pig CT > human CT, major differences were found when the absolute potencies of pig and human CT were compa red with salmon CT. For example, there was a 35-fold difference in the potency of pig CT, between the human CT receptor in T47D cells and th e recombinant pig CT receptor in transiently transfected cells. Human CT displayed negligible interaction with the pig CT receptor. Disparit ies in relative ligand potencies were maintained at the level of adeny late cyclase activation. The results show that CT receptors from diffe rent species cannot be regarded as a uniformly responding population a nd together with the recent cloning of pig, rat and human CT receptors , they provide a basis for exploring the structural determinants far C T receptor-ligand interaction.