Extrapituitary Expression of the Rat V1b Vasopressin Receptor Gene

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-07, Vol.92 (15), p.6783-6787
• Main Authors: Lolait, Stephen J., O'Carroll, Anne-Marie, Mahan, Lawrence C., Felder, Christian C., Button, Donald C., Young, W. Scott, Mezey, Eva, Brownstein, Michael J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Animals; Arginine Vasopressin - metabolism; Base Sequence; Binding, Competitive; Blotting, Northern; Blotting, Southern; Cellular biology; CHO cells; Complementary DNA; COS cells; Deoxyribonucleic acid; DNA; DNA, Complementary - genetics; Gene Library; GTP-Binding Proteins - metabolism; In Situ Hybridization; Inositol 1,4,5-Trisphosphate - metabolism; Messenger RNA; Molecular Sequence Data; Neurology; Pituitary gland; Pituitary Gland - metabolism; Polymerase Chain Reaction; Rats; Receptors; Receptors, Vasopressin - biosynthesis; Receptors, Vasopressin - genetics; Recombinant Proteins - biosynthesis; RNA; Rodents; Sequence Homology, Amino Acid; Tissue Distribution
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.15.6783

Arg8]vasopressin (AVP) stimulates adrenocorticotropic hormone release from the anterior pituitary by acting on the V1b AVP receptor. This receptor can be distinguished from the vascular/hepatic V1a and renal V2 AVP receptors by its differential binding affinities for structural analogous of AVP. Recent studies have shown that the cloned V1a and V2 receptors are structurally related. We have isolated a clone encoding the V1b receptor from a rat pituitary cDNA library using polymerase chain reaction (PCR)-based methodology. The rat V1b receptor is a protein of 421 amino acids that has 37-50% identity with the V1a and V2 receptors. Homology is particularly high in the seven putative membrane-spanning domains of these guanine nucleotide-binding protein-coupled receptors. Expression of the recombinant receptor in mammalian cells shows the same binding specificity for AVP agonists and antagonists as the rat pituitary V1b receptor. AVP-stimulated phosphotidylinositol hydrolysis and intracellular Ca2+mobilization in Chinese hamster ovary or COS-7 cells expressing the cloned receptor suggest second messenger signaling through phospholipase C. RNA blot analysis, reverse transcription PCR, and in situ hybridization studies reveal that V1b receptor mRNA is expressed in the majority of pituitary corticotropes as well as in multiple brain regions and a number of peripheral tissues, including kidney, thymus, heart, lung, spleen, uterus, and breast. Thus, the V1b receptor must mediate some of the diverse biological effects of AVP in the pituitary as well as other organs.