Acetylcholine and Norepinephrine Stimulate the Release of Corticotropin-Releasing Factor-41 from the Rat Hypothalamus<i>in Vitro</i>*

Tsagarakis, S.; Holly, Jeffrey M P; Rees, Lesley; Besser, G. M.; Grossman, Ashley

doi:10.1210/endo-123-4-1962

Cited by 119 publications

(57 citation statements)

References 36 publications

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“…Intracerebroventricular administration of CRF increases release of NE as measured by microdialysis probes sited in the medial hypothalamus (Lavicky and Dunn, 1993). This stimulatory effect of NE on CRF release has been observed in rat hypothalamic explants and was blocked by beta-adrenergic receptor antagonists, but not alpha adrenergic receptor blocking drugs (Tsagarakis et al, 1988). However, others (Suda et al, 1987) have reported decreased release of hypothalamic CRF after incubation of isolated hypothalamus with nanomolar concentrations of NE that were blocked by both alpha-and beta-adrenergic antagonists.…”

Section: Discussionmentioning

confidence: 90%

Elevated Concentrations of CRF in the Locus Coeruleus of Depressed Subjects

Bissette

Klimek

Pan

et al. 2003

Neuropsychopharmacol

130

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Research evidence that corticotropin-releasing factor (CRF) plays a role in the pathophysiology of major depressive disorder (MDD) has accumulated over the past 20 years. The elevation of lumbar cerebrospinal fluid (CSF) concentrations of CRF decreased responsiveness of pituitary CRF receptors to challenge with synthetic CRF, and increased levels of serum cortisol in MDD subjects support the hypothesis that CRF is chronically hypersecreted in at least the endocrine circuits of the hypothalamic-pituitary-adrenal (HPA) axis and may also involve other CRF brain circuits mediating emotional responses and/or arousal. One such circuit includes the excitatory CRF input to the locus coeruleus (LC), the major source of norepinephrine in the brain. Furthermore, there are now reports of decreased levels of CRF in lumbar CSF from MDD patients after symptom relief from chronic treatment with antidepressant drugs or electroconvulsive therapy. Whether this normalization reflects therapeutic effects on both endocrine-and limbic-associated CRF circuits has not yet been effectively addressed. In this brief report, we describe increased concentrations of CRF-like immunoreactivity in micropunches of post-mortem LC from subjects with MDD symptoms as established by retrospective psychiatric diagnosis compared to nondepressed subjects matched for age and sex.

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Section: Discussionmentioning

confidence: 90%

Elevated Concentrations of CRF in the Locus Coeruleus of Depressed Subjects

Bissette

Klimek

Pan

et al. 2003

Neuropsychopharmacol

130

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“…A recent microdialysis experiment (Tanaka et al, 1991) showed that the temporal profile of norepinephrine release from the amygdala of rats exposed to 20 min restraint stress closely matches that of CRF-IR described in the present work. In vitro norepinephrine evokes CRF-IR release from hypothalamic neurons (Tsagarakis et al, 1988;Hu et al, 1992), while microdialysis experiments show that CRF produces norepinephrine release from nerve terminals in prefrontal cortex and hypothalamus (Lavicky and Dunn, 1993), suggesting the existence of a reciprocal stimulating interaction between CRF and norepinephrine. Although the relevance of central norepinephrine in anxiety is still under debate, some of the behavioral effects produced by stress and ethanol withdrawal involve adrenoreceptor mediation (Berridge and Dunn, 1989;Glue et al, 1989;Soderpalm and Engel, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, 4-aminopyridine is known to release norepinephrine and acetylcholine in vitro (Drukarch et al, 1989;Heemskerk et al, 1990). Since norepinephrine or acetylcholine can produce CRF-IR release from the CNS neurons (Tsagarakis et al, 1988;Hu et al, 1992), it cannot be excluded that these or other neurotransmitters mediate the effects of 4-aminopyridine on CRF release within the amygdala.…”

Section: Discussionmentioning

confidence: 99%

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

et al. 1995

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Previous research has suggested a role for corticotropin-releasing factor (CRF) in the anxiogenic effects of stressful stimuli and ethanol withdrawal. This hypothesis was explored in a series of experiments using intracranial microdialysis to monitor CRF-like immunoreactivity (CRF-IR) in the extracellular compartment of the rat amygdala. The synaptic origin of CRF-IR release in the amygdala was determined in vitro by assessing the Ca2+ dependency of 4-aminopyridine stimulated CRF-IR release from tissue preparations of rat amygdala. In vivo experiments were performed in awake rats after the placement of microdialysis probes in the amygdala. In the first experiment, transient restraint stress (20 min) produced an increase of CRF-IR release (basal levels, 1.19 +/- 0.15 fmol/50 microliters; stress levels, 4.54 +/- 1.33 fmol/50 microliters; p < 0.05) that returned to basal values within 1 hr. When 4-aminopyridine (5 mM) was added to the perfusion medium, it consistently increased CRF-IR release (4.83 +/- 0.92 fmol/50 microliters, p < 0.05). In the second experiment, CRF-IR release was measured during ethanol withdrawal in rats previously maintained for 2–3 weeks on a liquid diet containing ethanol (8.5%). Basal CRF-IR levels were 2.10 +/- 0.43 fmol/50 microliters in ethanol exposed rats and 1.30 +/- 0.19 fmol/50 microliters in control rats. During withdrawal, a progressive increase of CRF-IR levels over time was observed, reaching peak values at 10–12 hr after the onset of withdrawal (10.65 +/- 0.49 fmol/50 microliters vs 1.15 +/- 0.30 fmol/50 microliters of control rats, p < 0.01).

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“…The system has been previously described in detail (16). Male Wistar rats (Banting & Kingham Ltd., Aldbrough, UK), specific pathogen free and weighing 200 to 300 g, were housed four per cage from weaning.…”

Section: Hyporhalumic Expiant Incubationmentioning

confidence: 99%

“…One recent study used a perifusion system of rat hypothalamic fragments to demonstrate a stimulatory role of clonidine on GHRH release (12), but a high concentration of clonidine was required to demonstrate the effect ( W 4 M ) , and no chromatographic characterization of G H R H was obtained. We have previously described a static hypothalamic incubation system for the study of somatostatin (I 3-15), gonadotrophin-releasing hormone (1 5) and corticotrophin-releasing factor-41 release (16), and have now used this system in conjunction with a new RIA for rat GHRH for the investigation of the adrenoceptor control of GHRH.…”

mentioning

confidence: 99%

Stimulation of Alpha‐Adrenoceptors Facilitates the Release of Growth Hormone‐Releasing Hormone from Rat Hypothalamus in vitro

Tsagarakis

Gao

Rees

et al. 1989

J Neuroendocrinology

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While extensive evidence suggests that adrenoceptors play a n important role in the control of growth hormone in the rat, there are few studies involving the direct measurement of growth hormone-releasing hormone (GHRH). We have therefore developed a radioimmunoassay for rat GHRH, and used it to investigate the modulation of GHRH release by noradrenaline from incubated rat hypothalamus in vitro. The GHRH radioimmunoassay had no significant cross-reactivity with other hypothalamic or GHRH-related peptides, and was sensitive to 4 pg/tube; intra-and interassay coefficients of variation were 6% and 12% respectively. Single incubated rat hypothalami produced a stable and readily measurable output of GHRH in successive 20 min incubations after an initial 60 min preincubation; the release of GHRH was increased in the presence of 56 mM KCI, but did not respond to KCIdepolarization when calcium was excluded from the medium. Stimulated GHRH release was identical to synthetic rat on high-performance liquid chromatography and Sephadex G-75 chromatography.Noradrenaline stimulated GHRH secretion in a dose-dependent manner in the concentration range lo-"-10-6M, with a plateau in response at 10-7M. Stimulation with noradrenaline 10-7M was blocked by idazoxan 10-5M and attenuated by thymoxamine 10-5M, but was unaffected by timolol 10-5M. Both the a,-adrenoceptor agonist guanfacine, and the a,-adrenoceptor agonist methoxamine, specifically stimulated GHRH secretion.It is concluded that noradrenaline stimulates the release of GHRH at both a l -and a,-adrenoceptors.It is now generally accepted that growth hormone (GH) release in the rat is under the control of two hypothalamic hormones, somatostatin and growth hormone-releasing hormone (GHRH). The latter was originally isolated and sequenced from two human pancreatic tumours ( I , 2), but the sequence of rat G H R H as a 43-residue peptide has more recently been identified (3). There is an extensive noradrenergic innervation to the rat hypothalamus (4), and depletion of central catecholamines abolishes the pulsatile release of G H (5).While there is some evidence that adrenaline may directly stimulate the release of pituitary somatotrophs, probably via Badrenoceptors (6, 7), extensive data exist on the adrenoceptor regulation of G H at central sites. Clonidine, a predominantly a2-adrenoceptor agonist, stimulates G H release in vivo (8); this effect is blocked by the a,-adrenoceptor antagonist yohimbine (8, 9), and is abolished in the presence of antiserum to G H R H (lo), but not to somatostatin (9). This suggests that the a,-adrenoceptors are directly stimulatory to G H R H neurons. Conversely, a,-adrenoceptor agonists such as methoxamine appear to inhibit G H release via somatostatin-mediated pathways (1 1). However, Krulich et al. (9) found that the effect of clonidine on G H release was partially antagonized by the a ,-adrenoceptor antagonist prazosin, and suggested that both aI-and a,-adrenoceptors were involved in the stimulation of G H release. Part of the difficul...

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Acetylcholine and Norepinephrine Stimulate the Release of Corticotropin-Releasing Factor-41 from the Rat Hypothalamusin Vitro*

Cited by 119 publications

References 36 publications

Elevated Concentrations of CRF in the Locus Coeruleus of Depressed Subjects

Elevated Concentrations of CRF in the Locus Coeruleus of Depressed Subjects

Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis

Stimulation of Alpha‐Adrenoceptors Facilitates the Release of Growth Hormone‐Releasing Hormone from Rat Hypothalamus in vitro

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