Cloning and characterization of the human corticotropin-releasing factor-2 receptor complementary deoxyribonucleic acid.

Abstract

Two CRF receptor subtypes (CRF1 and CRF2 receptors) with distinct brain localizations and pharmacological profiles have recently been cloned and characterized. For the CRF2 receptor subtype, at least 2 splice forms with different 5'-coding sequences (CRF2 alpha and CRF2 beta) have been identified in rat. In this article, we report the genomic structure and the corresponding complementary DNA (cDNA) sequence of the human CRF2 receptor. The gene coding for human CRF2 receptor consists of at least 12 exons and spans approximately 30 kilobases. The cDNA sequence in the protein-coding region is 94% identical to that of the reported rat CRF2 alpha receptor. At present, there is no evidence for the existence of a CRF2 beta receptor homolog in humans. The encoded receptor is 411 amino acids in length and is 70% identical to the human CRF1 receptor, with least sequence homology in the N-terminal extracellular domain (47% identical). Cells transfected with the full-length human CRF2 receptor cDNA responded to rat/human CRF and sauvagine by increasing the intracellular cAMP level, with EC50 values of approximately 20 and 1 nM, respectively. The CRF- and sauvagine-induced accumulation of intracellular cAMP could be competitively inhibited by the CRF receptor antagonist D-Phe-CRF. This pharmacological profile was comparable to that of the rat CRF2 alpha receptor. The relative abundance of the CRF2 receptor messenger RNA appears to be lower in humans than in rats for the tissues studied thus far.

Corticotropin-releasing hormone signaling in synovial tissue from patients with early inflammatory arthritis is mediated by the type 1? corticotropin-releasing hormone receptor

“…Two distinct subtypes of CRH receptors, CRH-R1 and CRH-R2, have been isolated and characterized in the human central nervous system (5,6) and are 68% homologous. Each subtype exhibits 2 alternatively spliced variants, displaying pharmacologically and functionally distinct isoforms (␣ and ␤) and exhibiting distinct central and peripheral tissue-specific expression patterns.…”

Urocortins in heart failure and ischemic heart disease

“…The CRF type2 (gamma) receptor has only been detected in the brain [38]. The cDNA sequence in the protein-coding region of rat tissue is 94% identical to the CRF type2 (beta) receptor [39,40]. The CRF type2 (beta) receptor has 10-fold higher affinity to urocortin than CRF in rat models [9], whereas the CRF type1 receptor shows little ligand selectivity for urocortin [10].…”

An intronic polymorphism in the corticotropin-releasing hormone receptor 2 gene increases susceptibility to HBV-related hepatocellular carcinoma in Chinese population

“…The human CRHR2 gene is located in the genomic region 7p21-p15 (Meyer et al 1997), spanning roughly 50 thousand base pairs (kbp) (Liaw et al 1996). The gene consists of 12 exons, and alternative splicing of the Wrst exon gives rise to three isoforms, CRHR2 , , and , which are distributed in the central nervous system (CNS) and periphery (Van Pett et al 2000;Muramatsu et al 2001;Kimura et al 2002).…”