TY - JOUR
T1 - Identification of a novel murine receptor for corticotropin-releasing hormone expressed in the heart
AU - Stenzel, Peter
AU - Kesterson, Robert
AU - Yeung, Wendy
AU - Cone, Roger D.
AU - Rittenberg, Marvin B.
AU - Stenzel-Poore, Mary P.
PY - 1995/5
Y1 - 1995/5
N2 - Corticotropin-releasing hormone (CRH) is the principal regulator of the stress response. CRH stimulates production of ACTH via specific CRH receptors located on pituitary corticotropes. In addition to pituitary and central nervous system effects, peripheral effects of CRH have been observed involving the immune and cardiovascular systems. Specific CRH binding studies in several peripheral organs, as well as functional studies, have implied the existence of peripheral CRH receptors. Although a pituitary/brain CRH receptor has recently been identified, it is expressed at very low levels in peripheral sites where CRH effects have been observed. We report here the identification of a novel murine CRH receptor that is highly expressed in the heart. The newly cloned CRH receptor cDNA (CRH-R2) was isolated from a mouse heart cDNA library and encodes a 430-amino acid protein containing seven putative transmembrane domains characteristic of G protein-coupled receptors. CRH-R2 is 69% identical with the previously identified murine pituitary CRH receptor and is encoded by a distinct gene. In addition to a high level of expression in the heart, weak expression was also observed in the brain and lungs. Functional studies using CRH-R2-transfected cells indicate that CRH and the CRH-related amphibian peptide, sauvagine, bind with high affinity to CRH-R2 and stimulate intracellular accumulation of cAMP. Interestingly, sauvagine bound CRH-R2 at an affinity 50-fold higher than CRH, an important finding in light of sauvagine's greater potency in mediating hypotensive effects in the peripheral vascular system. Thus, this new receptor represents the first CRH receptor expressed at high levels in the periphery and may mediate the effects of CRH in cardiac function and the response to stress.
AB - Corticotropin-releasing hormone (CRH) is the principal regulator of the stress response. CRH stimulates production of ACTH via specific CRH receptors located on pituitary corticotropes. In addition to pituitary and central nervous system effects, peripheral effects of CRH have been observed involving the immune and cardiovascular systems. Specific CRH binding studies in several peripheral organs, as well as functional studies, have implied the existence of peripheral CRH receptors. Although a pituitary/brain CRH receptor has recently been identified, it is expressed at very low levels in peripheral sites where CRH effects have been observed. We report here the identification of a novel murine CRH receptor that is highly expressed in the heart. The newly cloned CRH receptor cDNA (CRH-R2) was isolated from a mouse heart cDNA library and encodes a 430-amino acid protein containing seven putative transmembrane domains characteristic of G protein-coupled receptors. CRH-R2 is 69% identical with the previously identified murine pituitary CRH receptor and is encoded by a distinct gene. In addition to a high level of expression in the heart, weak expression was also observed in the brain and lungs. Functional studies using CRH-R2-transfected cells indicate that CRH and the CRH-related amphibian peptide, sauvagine, bind with high affinity to CRH-R2 and stimulate intracellular accumulation of cAMP. Interestingly, sauvagine bound CRH-R2 at an affinity 50-fold higher than CRH, an important finding in light of sauvagine's greater potency in mediating hypotensive effects in the peripheral vascular system. Thus, this new receptor represents the first CRH receptor expressed at high levels in the periphery and may mediate the effects of CRH in cardiac function and the response to stress.
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U2 - 10.1210/me.9.5.637
DO - 10.1210/me.9.5.637
M3 - Article
C2 - 7565810
AN - SCOPUS:0029010906
SN - 0888-8809
VL - 9
SP - 637
EP - 645
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 5
ER -