EXTRAPITUITARY EXPRESSION OF THE RAT V1B VASOPRESSIN RECEPTOR GENE

[Arg(8)]vasopressin (AVP) stimulates adrenocorticotropic hormone relea se 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 structura l analogous of AVP. Recent studies have shown that the cloned Via and V2 receptors are structurally related. We have isolated a clone encodi ng the V1b receptor from a rat pituitary cDNA library using polymerase chain reaction (PCR)-based methodology. The rat V1b receptor is a pro tein of 421 amino acids that has 37-50% identity with the Via and V2 r eceptors. 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 s hows the same binding specificity for AVP agonists and antagonists as the rat pituitary V1b receptor. AVP-stimulated phosphotidylinositol hy drolysis 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 transcr iption 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, inclu ding kidney, thymus, heart, lung, spleen, uterus, and breast. Thus, th e V1b receptor must mediate some of the diverse biological effects of AVP in the pituitary as well as other organs.