The central distribution of a corticotropin-releasing factor (CRF)-binding protein predicts multiple sites and modes of interaction with CRF.

Potter, Ellen; Behan, Dominic P.; Linton, Elizabeth A.; Lowry, P. J.; Sawchenko, Paul E.; Vale, Wylie

doi:10.1073/pnas.89.9.4192

Cited by 267 publications

(223 citation statements)

References 21 publications

(24 reference statements)

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“…(ii) The distribution of CRF2 receptor mRNA shows a unique highly localized distribution in the brain, with prominant expression in the limbic regions. This is in contrast to CRF1 receptor (14) or the CRF-binding protein (28), which are both widely and somewhat codistributed throughout the brain, particularly in cerebral cortex and in pituitary. In accordance with these findings, it can be hypothesized that different aspects of CRF physiology may be altered by drugs displaying selectivity for CRF1 vs. CRF2 receptors.…”

Section: Discussionmentioning

confidence: 99%

Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain.

Lovenberg

Liaw

Grigoriadis

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

800

473

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The present study reports the isolation of a cDNA clone that encodes a second member of the corticotropin-releasing factor (CRF) receptor family, designated as the CRF2 receptor. The cDNA was identified using oligonucleotides of degenerate sequence in a PCR paradigm. A PCR fragment obtained from rat brain was utilized to isolate a full-length cDNA from a rat hypothalamus cDNA library that encoded a 411-amino acid protein with "70% identity to the known CRF1 receptor over the entire coding region. When expressed in mouse Ltk-cells, this receptor stimulates cAMP production in response to CRF and known CRF-like agonists. CRF and the nonmammalian CRF-related peptides sauvagine and urotensin I stimulate adenylate cyclase activity in a dose-dependent manner with a rank order of potency different from that of the CRF1 receptor: sauvagine > urotensinrat/human CRF > ovine CRF. Tissue distribution analysis of the mRNAs by reverse transcriptase-PCR shows CRF2 receptor mRNA is present in rat brain and detectable in lung and heart. In situ hybridization studies indicate specific expression within the brain in the ventromedial nuclei of the hypothalamus, the lateral septum, the amygdala, and entorhinal cortex, but there is unremarkable expression in the pituitary. An additional splice variant of the CRF2 receptor with a different N-terminal domain has been identified by PCR, encoding a putative protein of 431 amino acids. Thus, the data demonstrate the presence of another functional CRF receptor, with significant differences in the pharmacological profile and tissue distribution from the CRF1 receptor, which would predict important functional differences between the two receptors.Corticotropin-releasing factor (CRF), a 41-amino acid peptide, regulates the secretion of adrenocorticotropin and other proopiomelanocortin products from the anterior pituitary. CRF also coordinates the endocrine, behavioral, and autonomic responses to stress. Within the past few years, substantial evidence has accumulated from both laboratory and clinical studies implicating CRF as a physiological mediator of stress responses and stress-induced disorders (1-6). Immunocytochemical studies have shown that CRF is found within the paraventricular nucleus of the hypothalamus as well as limbic areas such as the central and medial nuclei of the amygdala, the bed nucleus of the stria terminalis, substantia inominata, septum, preoptic area, the lateral hypothalamus, and brain stem nuclei involved in stress responses and regulation of autonomic function, such as the locus coeruleus, the parabrachial nucleus, and the dorsal vagal complex (see ref. 7). CRF, when administered intracerebroventricularly, results in behavioral, physiological, and autonomic responses that are similar to those observed when animals are exposed to a stressful environment (4-6).

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Section: Discussionmentioning

confidence: 99%

Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain.

Lovenberg

Liaw

Grigoriadis

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

800

473

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“…Autoradiography and radioligand binding studies during early postnatal life in the rat have demonstrated changes in receptor number and regional distribution [5,6,11,12,15]. The two methods have yielded conflicting information regarding CRH receptor distribution in a number of brain regions [12,16,17]. A potential basis for this discrepancy derives from CRH binding protein which may interact with the CRH ligand [12,16].…”

Section: Introductionmentioning

confidence: 99%

“…The two methods have yielded conflicting information regarding CRH receptor distribution in a number of brain regions [12,16,17]. A potential basis for this discrepancy derives from CRH binding protein which may interact with the CRH ligand [12,16]. Binding studies may also provide limited information on the actual site of receptor synthesis because ligands may bind to neural receptors on cell bodies and along dendrites and axons [17].…”

Section: Introductionmentioning

confidence: 99%

Developmental profile of messenger RNA for the corticotropin-releasing hormone receptor in the rat limbic system

Avishai-Eliner

Baram

1996

Developmental Brain Research

101

110

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The ontogeny of corticotropin-releasing hormone (CRH) receptor messenger ribonucleic acid (mRNA) in rat brain, using in situ hybridization, is the focus of this study. The developmental profile of CRH receptor using binding assays and receptor autoradiography has been reported, but may be confounded by the presence of a binding protein. The recent cloning of the rat CRH receptor gene has permitted the use of in situ hybridization histochemistry to map the distribution of cells expressing CRH receptor mRNA in the developing brain. We used antisense 35 S-labeled oligodeoxynucleotide probes for the two reported splice-variants of the CRH receptor mRNA, which yielded essentially identical localization patterns. CRH receptor mRNA was clearly detectable in infant brain starting on the second postnatal day. Signal in hippocampal CA1, CA2 and CA3a increased to 300-600% of adult levels by postnatal day 6 with a subsequent gradual decline. In the amygdala, in contrast, CRH receptor mRNA abundance increased steadily between the second and the ninth postnatal days, to levels twice higher than those in the adult. In the cortex, CRH receptor mRNA levels were high on postnatal day 2 and decreased to adult levels by day 12. Transient signal over the hypothalamic paraventricular nucleus, observed on the second postnatal day, was not evident at older ages. These results demonstrate robust synthesis of CRH receptor as early as on the second postnatal day and unique region-specific developmental profiles for CRH receptor gene expression.

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“…Indeed, several studies favor the involvement of CRF 2 receptors in regulating DRN functions, especially in the more caudal regions of the DRN (Hammack et al, 2003, Staub et al, 2006. Additionally, CRF binding protein (CRF-BP) has been reported to modulate the availability of CRF family peptides (Potter et al, 1992, Seasholtz et al, 2002. oCRF and rat UCNII may have different affinities for CRF-BP.…”

mentioning

confidence: 99%

“…Unfortunately, our results do not provide strong evidence to favor the role of one CRF receptor over another in their actions on serotonergic neurons and behavior described in this paper. Furthermore, CRF binding protein is present in the DRN and could modulate the availability of CRF family neuropeptides there (Potter et al, 1992, Seasholtz et al, 2002 thus altering local peptide concentrations. More specific pharmacologic and transgenic experiments should help clarify the roles of each receptor type as well as CRF-BP in the DRN.…”

mentioning

confidence: 99%

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

et al. 2007

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Corticotropin releasing factor (CRF) family peptides play key roles in integrating neural responses to stress. Both major CRF receptors have been pharmacologically identified in the dorsal raphe nucleus (DRN), a stress sensitive and internally heterogeneous nucleus supplying many forebrain regions with serotonergic input. Despite the involvement of chronic stress and serotonergic dysfunction in human mood and anxiety disorders, little is known about the effects of chronic CRF receptor activation on the DRN. We infused ovine CRF (1ng/hr), urocortin II (UCNII, 1ng/hr), or vehicle alone into rat DRN over 6 days. During infusion, animals were allowed to freely explore an open field for 15 minutes on each of two days, with the addition of a novel object on the second day. Following behavioral testing, 5-HT 1A , 5-HT 1B , serotonin transporter (SERT), and tryptophan hydroxylase-2 (Tph2) expression were examined through the DRN by in situ hybridization. Ovine CRF infusion resulted in significantly decreased novel object touches, climbs, as well as increased latency to first novel object contact. UCNII had a similar but less dramatic effect, decreasing only climbing behavior. Both ovine CRF and UCNII blunted the decrease in corner time expected on reexposure to the open field. Both peptides also produced regionally specific changes in gene expression: 5-HT 1A expression was increased 30% in the mid-rostral ventromedial DRN, while SERT was decreased by 30% in the mid-caudal shell dorsomedial DRN. There also appeared to be a shift in the relative level of Tph2 expression between the ventromedial and core dorsomedial DRN at the mid-rostral level. Changes in 5-HT 1A , SERT, and relative Tph2 mRNA abundance were correlated with novel object exploration. These findings suggest chronic intra-DRN administration of CRF agonists decreases exploratory behavior, while producing subregionally limited changes in serotonergic gene expression. These studies may be relevant to mechanisms underlying behavioral changes after chronic stress. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptDepression and anxiety disorders are among the leading causes of morbidity, mortality, and disability in the United States (Greenberg et al., 2003). They are often comorbid, and both are highly associated with chronic exposure to stress. Multiple lines of evidence suggest that chronic and inescapable stress produce long lasting effects on brain function and behavior that play a prominent role in the development, maintenance, and recurrence of both depression and a variety of anxiety disorders (Gulley and Nemeroff, 1993, Arborelius et al., 1999, Ressler and Nemeroff, 2000.Altered serotonin neurotransmission appears to be a central mechanism inducing both depressive (Maes and Meltzer, 1995) and anxiety disorders (Ressler and Nemeroff, 2000). The majority of serotonergic fibers to forebrain regions thought to be involved in mood and anxiety regulation arise from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) ...

show abstract

The central distribution of a corticotropin-releasing factor (CRF)-binding protein predicts multiple sites and modes of interaction with CRF.

Cited by 267 publications

References 21 publications

Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain.

Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain.

Developmental profile of messenger RNA for the corticotropin-releasing hormone receptor in the rat limbic system

Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

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