Central stresscopin modulates cardiovascular function through the adrenal medulla in conscious rats

Chu, Chun-Ping; Qiu, De-Lai; Kato, Kazuo; Kunitake, Takato; Watanabe, Shōichi; Yu, Nengwang; Nakazato, Masamitsu; Kannan, Hiroshi

doi:10.1016/j.regpep.2003.12.007

Cited by 26 publications

(19 citation statements)

References 54 publications

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“…In agreement with this suggestion, observations in sheep indicate that CRFmediated pituitary-adrenal activation has no concomitant hemodynamic effects (Parkes et al, 1997). Furthermore, since central administration of CRF causes pressor and mesenteric vasoconstrictor effects (Grosskreutz and Brody, 1988;Overton and Fisher, 1991), and central administration of hUCN3 causes a rise rather than a fall in blood pressure (Chu et al, 2004), whereas we saw frank hypotension and mesenteric vasodilatation with hUCN2, it is unlikely that centrally mediated effects played a major part in the responses reported here. However, we cannot dismiss the possibility that there was a central component to some of the effects we observed since tachycardia and hindquarters vasodilatation can occur after central, as well as peripheral, administration of CRF (Overton and Fisher, 1991).…”

Section: Discussionsupporting

confidence: 90%

Regional Hemodynamic Actions of Selective Corticotropin-Releasing Factor Type 2 Receptor Ligands in Conscious Rats

Gardiner

March²,

Kemp³

et al. 2004

J Pharmacol Exp Ther

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In conscious male Sprague-Dawley rats, we compared regional hemodynamic actions of the selective corticotropin-releasing factor type 2 (CRF 2 ) receptor ligands human and mouse urocortin 2 (hUCN2 and mUCN2, respectively) with those of CRF. Bolus i.v. doses of 3 and 30 pmol kg Ϫ1 hUCN2, mUCN2, or CRF had no significant hemodynamic actions, but at doses of 300 and 3000 pmol kg Ϫ1 , all three peptides caused dosedependent tachycardia and hypotension, with rapid-onset, short-duration, mesenteric vasodilatation and slower-onset, more prolonged hindquarters vasodilatation but little or no change in renal vascular conductance. Pretreatment with the nonselective CRF receptor antagonist astressin or the selective CRF 2 receptor antagonist antisauvagine 30 abolished all the cardiovascular actions of all three peptides. Indomethacin had no effect on responses to hUCN2, and there was no evidence for any involvement of nitric oxide (NO) in the vasodilator actions of hUCN2. There was no evidence that recruitment of angiotensin-and endothelin-mediated vasoconstrictor mechanisms counteracted the vascular actions of hUCN2. The results indicate that the hemodynamic effects of i.v. hUCN2, mUCN2, and CRF depend on activation of CRF 2 receptors and do not involve NO or prostanoids.

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Section: Discussionsupporting

confidence: 90%

Regional Hemodynamic Actions of Selective Corticotropin-Releasing Factor Type 2 Receptor Ligands in Conscious Rats

Gardiner

March²,

Kemp³

et al. 2004

J Pharmacol Exp Ther

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“…Similar inconsistencies exist in studies demonstrating differentially modulated hormonal stress responses (22,(26)(27)(28). Our data demonstrate a relationship between the integrative actions of all urocortins in modulating stress responses.…”

Section: (G and H) Asr (G)supporting

confidence: 80%

A triple urocortin knockout mouse model reveals an essential role for urocortins in stress recovery

Neufeld-Cohen

Tsoory²,

Evans³

et al. 2010

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

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Responding to stressful events requires numerous adaptive actions involving integrated changes in the central nervous and neuroendocrine systems. Numerous studies have implicated dysregulation of stress-response mechanisms in the etiology of stress-induced psychopathophysiologies. The urocortin neuropeptides are members of the corticotropin-releasing factor family and are associated with the central stress response. In the current study, a tripleknockout (tKO) mouse model lacking all three urocortin genes was generated. Intriguingly, these urocortin tKO mice exhibit increased anxiety-like behaviors 24 h following stress exposure but not under unstressed conditions or immediately following exposure to acute stress. The inability of these mutants to recover properly from the exposure to an acute stress was associated with robust alterations in the expression profile of amygdalar genes and with dysregulated serotonergic function in stress-related neurocircuits. These findings position the urocortins as essential factors in the stress-recovery process and suggest the tKO mouse line as a useful stress-sensitive mouse model. amygdala | anxiety-like behaviors | serotonergic system | corticotropinreleasing factor | corticotropin-releasing factor receptor type 2 D ysregulation of stress-response mechanisms is proposed to underlie a variety of stress-related psychopathologies (1, 2). Corticotropin-releasing factor (CRF) plays a pivotal and wellestablished role in regulating the hypothalamic-pituitary-adrenal (HPA) axis under basal and stress conditions (3, 4) and, via its type 1 receptor (CRFR1), integrates the autonomic, metabolic and behavioral stress responses (5).The CRF peptide family includes also three urocortin (Ucn) peptides (Ucn1, Ucn2, and Ucn3) that bind and activate the CRF receptor type 2 (CRFR2) with high affinity (6-12). CRF has a relatively lower affinity for CRFR2 than for CRFR1; Ucn1 has equal affinities for both; and Ucns 2 and 3 appear to be selective for CRFR2 (6-9). These receptors are distributed differently throughout the brain: CRFR1 is widely expressed in various brain regions, whereas CRFR2 expression is more localized to selected stress-related brain nuclei, such as the amygdala, the bed nucleus of the stria terminalis (BNST), the lateral septum (LS), and the dorsal raphe nucleus (DRN) (13,14).Evidence from studies using competitive peptides or smallmolecule CRF/urocortin receptor antagonists suggested that the brain CRF/urocortin systems play diverse roles in mediating behavioral responses to stress (15). Based on the complementary behavioral phenotypes of CRFR1-and CRFR2-deficient (KO) mice, opposing roles were suggested for the two CRF receptors systems in modulating anxiety-like behaviors. CRFR1KO mice display decreased anxiety-like behaviors coupled with an impaired HPA axis stress response (16, 17), whereas CRFR2KO mice show increased anxiety-like behaviors and an accelerated HPA-axis response to stress (18,19). Thus, the CRF-CRFR1 system has been suggested as critical for initiating str...

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“…Previous studies have shown that Ucn3 regulates cardiovascular and immune functions via the CRF receptors. ICV administration of Ucn3 increased blood pressure and heart rate [14]. In addition, peripherally administered Ucn3 influenced steroidogenesis and cell proliferation [15].…”

Section: Introductionmentioning

confidence: 99%

Centrally administered urocortin 3 inhibits food intake and gastric emptying in mice

Ushikai

Asakawa

Sakoguchi

et al. 2010

Endocr

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Urocortin 3 (Ucn3) is recognized as a member of the corticotropin-releasing factor (CRF) family, which plays an important role in regulating food intake. We investigated the effects of centrally administered Ucn3 on food intake and gastric emptying in mice. Intracerebroventricular (ICV)administration of Ucn3 (0.1–1 nmol per mouse) decreased food intake in a dose-dependent manner. The inhibitory effect of Ucn3 on food intake was less potent than that of centrally administered CRF and Urocortin 1. ICV administration of Ucn3 (0.1–1 nmol per mouse) decreased the gastric emptying rate in a dose-dependent manner. Ucn3 decreased food intake in high-fat diet-fed obese mice as well as in lean mice. These results indicated that Ucn3 influences feeding behavior and gut motility, and may be a promising therapeutic target in the treatment of eating and functional gastrointestinal disorders.

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Central stresscopin modulates cardiovascular function through the adrenal medulla in conscious rats

Cited by 26 publications

References 54 publications

Regional Hemodynamic Actions of Selective Corticotropin-Releasing Factor Type 2 Receptor Ligands in Conscious Rats

Regional Hemodynamic Actions of Selective Corticotropin-Releasing Factor Type 2 Receptor Ligands in Conscious Rats

A triple urocortin knockout mouse model reveals an essential role for urocortins in stress recovery

Centrally administered urocortin 3 inhibits food intake and gastric emptying in mice

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