Résumé : The role in ligand recognition and receptor activation of two adjacent charged residues (lysine 195 and aspartate 196) in the first extracellular loop of the human VPAC(1) receptor was investigated in stably transfected CHO cells expressing the wild type or point mutated receptors.Replacement of lysine 195 by glutamine or of aspartate 196 by asparagine reduced the agonists' ability to stimulate adenylate cyclase activity; VIP behaved like a partial agonist and a partial agonist behaved as an antagonist. The receptor's capacity to recognize agonists was reduced but antagonists' affinity was unaffected. Both results suggesting that the two charged residues are essential for VPAC(1) receptor activation. On the other hand, the double mutant was less severely affected than single mutants suggesting that hydrogen bonds may partially compensate the loss of charged residues. But the inversion of the residues affected receptor recognition and activation more markedly suggesting that the two charged residues do not interact directly.