Cloning and characterization of corticotropin-releasing factor and urocortin in Syrian hamster (Mesocricetus auratus)

Corticotropin-releasing factor and urocortin belong to a superfamily of neu ropeptides that includes the urotensins-I in fishes and the insect diuretic peptides. Sequence analysis suggests that urocortin is the mammalian ortho log of urotensin-l, although the physiological role for this peptide in mam mals is not known. Within the Rodentia, hamsters belong to a phylogenetical ly older lineage than that of mice and rats and possess significant differe nces in hypothalamic organization. We have, therefore, cloned the coding re gion of the Syrian hamster (Mesocricetus auratus) corticotropin-releasing f actor and urocortin mature peptide by polymerase chain reaction. Hamster ur ocortin was prepared by solid-phase synthesis, and its pharmacological acti ons on human corticotropin-releasing factor R1 and R2 receptors were invest igated. The deduced hamster corticotropin-releasing factor amino acid seque nce and cleavage site is identical to that in rat, whereas the urocortin se quence is unique among the urocortin/urotensin-I/sauvagine family in posses sing asparagine and alanine in positions 38 and 39, respectively. The hamst er urocortin carboxy terminus sequence bears greater structural similarity to the insect diuretic peptide family, suggesting either retrogressive muta tional changes within the mature peptide or convergent sequence evolution. Despite these changes, human and hamster urocortin are generally equipotent at cAMP activation, neuronal acidification rate, and R1/R2 receptor affini ties. (C) 1999 Elsevier Science Inc. All rights reserved.