Properties of a recombinant human secretin receptor: A comparison with therat and rabbit receptors

A secretin receptor was cloned from a commercial human pancreatic complemen tary DNA (cDNA) bank. The amino acid sequence deduced from the nucleotide s equence differed slightly from the three different sequences previously pub lished, suggesting a genetic polymorphism of the human receptor. The bindin g properties of the receptor were evaluated by testing natural secretin, re lated peptides, and synthetic analogs or fragments on membranes of Chinese hamster ovary (CHO) cells expressing the receptor after transfection. The s econd-messenger coupling was evaluated by adenylate cyclase measurement. Th e human secretin receptor was compared with the rat and the rabbit receptor s. In the three animals species, rat and human secretin were equipotent; ra bbit secretin was equi-potent on human and rabbit secretin receptors and le ss potent on the rat receptor. Similar data were obtained for the [Arg(16)] -secretin analog. Deletion of histidine 1 and replacement of aspartate 3 re duced the affinity of the peptides for the three receptors; however, the re duction was more pronounced on rat than on human and rabbit secretin recept ors. Finally, the low affinity of the rat and human receptors for vasoactiv e intestinal peptide (VIP) was identical; the rabbit receptor, however, had a 20-fold higher affinity. Thus the human secretin receptor shows properti es of both rat and rabbit receptors. Evaluation of the properties of chimer ic receptors will be useful to fit the ligand on the receptors.