Attenuation of corticotropin releasing factor-induced hypotension in anesthetized rats with the CRF antagonist, α-helical CRF9–41; Comparison with effect on ACTH release

Corder, Roger; Turnill, D.; Ling, N; Gaillard, Rolf C.

doi:10.1016/0196-9781(92)90132-m

Cited by 27 publications

(18 citation statements)

References 21 publications

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“…), as well as another aminopyrazole CRH1 antagonist, did not reduce either the magnitude or the duration of the CRH-induced hypotension in anesthetized male Sprague-Dawley rats (S. Gonsalves, unpublished data). In agreement with Corder et al (30) ah-CRH (50 nmol, i.v.) completely blocked this response, suggesting that it may be CRH2-receptor-mediated.…”

Section: Effects On Autonomic Nervous Systemsupporting

confidence: 80%

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The Pharmacology of CP‐154,526, a Non‐Peptide Antagonist of the CRH1 Receptor: A Review

2003

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Since CRH has been shown to mediate stress-induced physiological and behavioral changes, it has been hypothesized that CRH receptor antagonists may have therapeutic potential in disorders that involve excessive CRH activity. CP-154,526 and its close analog antalarmin are potent, brain-penetrable, selective nonpeptide CRH1 receptor antagonists that were discovered in an effort to develop compounds with efficacy in CNS disorders precipitated by stress. Since its discovery many investigators have used CP-154,526 as a tool to study the pharmacology of CRH and its receptors and to evaluate its therapeutic potential in a variety of CNS and peripheral disorders. Systemically-administered CP-154,526 has been demonstrated to antagonize CRH-and stress-induced neuroendocrine, neurochemical, electrophysiological, and behavioral effects.These findings support the hypothesis that CRH1 receptor antagonists may have therapeutic utility in a number of neuropsychiatric disorders. CP-154,526, as well as other CRH1 receptor antagonists that have since been discovered, have also shown activity in several preclinical models of anxiety, depression, and substance abuse, while having little effect on locomotor activity and motor function. Although these effects are on occasion inconsistent among different laboratories, clinical evaluation of CRH1 antagonists appears justified on the basis of these and clinical data implicating the involvement of CRH in several CNS disorders. The effects of CRH1 antagonists on cognition, neurodegeneration, inflammation, and the gastrointestinal system have not been as extensively characterized and additional studies will be necessary to evaluate their therapeutic potential in these areas.

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Section: Effects On Autonomic Nervous Systemsupporting

confidence: 80%

“…By i.v. administration, however, CRH produces a hypotensive effect (30). This latter effect was blocked by ah-CRH.…”

Section: Effects On Autonomic Nervous Systemmentioning

confidence: 91%

The Pharmacology of CP‐154,526, a Non‐Peptide Antagonist of the CRH1 Receptor: A Review

2003

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“…In vivo, the CRF antagonist, ahel CRF-(9-41), is a more potent inhibitor of CRF-induced hypotension and tachycardia than of CRF-induced elevations of plasma ACTH and 13-endorphin (30,31). In accordance with those studies, our results show that the antagonist ahel CRF-(9-41) is more potent in inhibiting HM-CRF receptor-rather than PC-CRF receptormediated cAMP response.…”

Section: E-qe--neekkskv--h--v-i-supporting

confidence: 80%

A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle

1995

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

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Corticotropin-releasing factor (CRF) mediates many critical aspects of the physiological response to stress. These effects are elicited by binding to specific highaffinity receptors, which are coupled to guanine nucleotide stimulatory factor (Gs)-response pathways. Recently, a gene encoding a receptor for CRF, expressed in pituitary and the central nervous system (PC-CRF receptor), was isolated and characterized. Here we report the identification and characterization of a second, distinct CRF receptor that is expressed primarily in heart and skeletal muscle and exhibits a specific ligand preference and antagonist sensitivity compared with the PC-CRF receptor. We refer to this second receptor as the heart/muscle (HM)-CRF receptor.Corticotropin-releasing factor (CRF) (1) is a member of a family of peptides from different species that act as agonists of the CRF receptor. These peptides include the frog skin peptide, sauvagine (2), and the teleost fish urophysis peptide, urotensin I (3). CRF is a 41-amino acid hypothalamic neuropeptide that plays a central role in coordinating the communications between endocrine, nervous, and immune systems to achieve homeostasis in response to environmental adversities (4, 5). The peptide was originally characterized in the hypothalamo-hypophyseal system but was later found to be widely distributed throughout the central nervous system (CNS), where it appeared to function as a neurotransmitter or neuromodulator (6). In the CNS, CRF initiates the hypothalamic-pituitary-adrenal axis by stimulating the release of adrenocorticotropin (ACTH) and ,B-endorphin from the anterior pituitary. ACTH stimulates adrenal cortex to secrete corticosteroids that, in turn, elicit a wide range of biological responses and exert negative feedback on the hypothalamus and pituitary (4, 5, 7). Both sauvagine and urotensin I have been shown to stimulate the hypothalamic-pituitary-adrenal axis after i.v. administration (8). Intracerebroventricular administration of CRF provokes stress-like responses including activation of the sympathetic nervous system, resulting in an elevation of plasma epinephrine, norepinephrine, and glucose, which results in increased heart rate and mean arterial blood pressure (9, 10). Outside the CNS, CRF immunoreactivity is detectable in multiple peripheral organs, including placenta, adrenal medulla, pancreas, lung, stomach, duodenum, and liver (4, 5). i.v. administration of CRF, sauvagine, and urotensin I has been shown to elicit peripheral systemic responses, including vasodilation (11).CRF functions by binding to a membrane-bound receptor that is coupled to the guanine nucleotide stimulatory factor (G,) signaling protein, resulting in increased intracellular cAMP levels (12,13 (23), and growth hormonereleasing factor ]. The PC-CRF receptor mRNA was found to be most highly expressed in the cerebellum and pituitary and found at lower levels in other brain areas, intestine, and testes. This receptor is undetectable in other tissues examined, including heart and skeletal mus...

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“…[1][2][3] These responses are associated with sustained vasodilatation in a number of tissues. 1,2 Recent investigations of the underlying mechanisms of these responses using isolated preparations have shown the vasodilator effect of CRF to involve both a direct action on vascular smooth muscle and a prolonged endothelium-dependent response due to the sustained release of nitric oxide (NO).…”

Section: Introductionmentioning

confidence: 99%

Corticotrophin releasing factor attenuates NG-Nitro-L-arginine Methyl Ester induced increases in blood pressure in the anaesthetised rat

Corder

1999

J Hum Hypertens

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Attenuation of corticotropin releasing factor-induced hypotension in anesthetized rats with the CRF antagonist, α-helical CRF9–41; Comparison with effect on ACTH release

Cited by 27 publications

References 21 publications

The Pharmacology of CP‐154,526, a Non‐Peptide Antagonist of the CRH1 Receptor: A Review

The Pharmacology of CP‐154,526, a Non‐Peptide Antagonist of the CRH1 Receptor: A Review

A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle

Corticotrophin releasing factor attenuates NG-Nitro-L-arginine Methyl Ester induced increases in blood pressure in the anaesthetised rat

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