Identification of a novel V1-type AVP receptor based on the molecular recognition theory.
BACKGROUND
The molecular recognition theory predicts that binding domains of peptide hormones and their corresponding receptor binding domains evolved from complementary strands of genomic DNA, and that a process of selective evolutionary mutational events within these primordial domains gave rise to the high affinity and high specificity of peptide hormone-receptor interactions observed today in different peptide hormone-receptor systems. Moreover, this theory has been broadened as a general hypothesis that could explain the evolution of intermolecular protein-protein and intramolecular peptide interactions.


METHODS
Applying a molecular cloning strategy based on the molecular recognition theory, we screened a rat kidney cDNA library with a vasopressin (AVP) antisense oligonucleotide probe, expecting to isolate potential AVP receptors.


RESULTS
We isolated a rat kidney cDNA encoding a functional V1-type vasopressin receptor. Structural analysis identified a 135 amino acid-long polypeptide with a single transmembrane domain, quite distinct from the rhodopsin-based G protein-coupled receptor superfamily. Functional analysis of the expressed V1-type receptor in Cos-1 cells revealed AVP-specific binding, AVP-specific coupling to Ca2+ mobilizing transduction system, and characteristic V1-type antagonist inhibition.


CONCLUSIONS
This is the second AVP receptor cDNA isolated using AVP antipeptide-based oligonucleotide screening, thus providing compelling evidence in support of the molecular recognition theory as the basis of the evolution of this peptide hormone-receptor system, as well as adds molecular complexity and diversity to AVP receptor systems.
Herrera
V L
VL
Section of Molecular Genetics, Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts 02118, USA.
Ruiz-Opazo
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D019143:Evolution, Molecular; D015870:Gene Expression; D007700:Kinetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D051381:Rats; D017483:Receptors, Vasopressin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
D018076:DNA, Complementary; D017483:Receptors, Vasopressin; D011994:Recombinant Proteins