Transport of CRH from mouse brain directly affects peripheral production of β-endorphin by the spleen

Martins, João Martin; Banks, William A.; Kastin, Abba J.

doi:10.1152/ajpendo.1997.273.6.e1083

Cited by 24 publications

(20 citation statements)

References 34 publications

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“…Blood-brain barrier transports specific peptides from the brain to the periphery (20). Central injection of radioactively labeled CRH accumulates in the spleen and releases ␤-endorphin (25). However, our findings show that the plasma levels of CRH do not increase in response to HeCS.…”

Section: Discussionmentioning

confidence: 51%

Norepinephrine mediates the transcriptional effects of heterotypic chronic stress on colonic motor function

Choudhury¹,

Shi²,

Sarna³

2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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Chronic stress precipitates or exacerbates the symptoms of functional bowel disorders, including motility dysfunction. The cellular mechanisms of these effects are not understood. We tested the hypothesis that heterotypic chronic stress (HeCS) elevates the release of norepinephrine from the adrenal medulla, which enhances transcription of the gene-regulating expression of Ca(v)1.2 (L-type) channels in colonic circular smooth muscle cells, resulting in enhanced colonic motor function. The experiments were performed in rats using a 9-day heterotypic chronic stress (HeCS) protocol. We found that HeCS, but not acute stress, time dependently enhances the contractile response to ACh in colonic circular smooth muscle strips and in single dissociated smooth muscle cells, the plasma levels of norepinephrine and the mRNA and protein expressions of the alpha(1C) subunit of Ca(v)1.2 channels. These effects result in faster colonic transit and increase in defecation rate. The effects of HeCS are blocked by adrenalectomy but not by depletion of norepinephrine in sympathetic neurons. The inhibition of receptors for glucocortocoids, corticotropin-releasing hormone or nicotine also does not block the effects of heterotypic chronic stress. Norepinephrine acts on alpha- and beta(3)-adrenergic receptors to induce the transcription of alpha(1C) subunit. We conclude that HeCS alters colonic motor function by elevating the plasma levels of norepinephrine. Colonic motor dysfunction is associated with enhanced gene transcription of Ca(v)1.2 channels in circular smooth muscle cells. These findings suggest the potential cellular mechanisms by which heterotypic chronic stress may exacerbate motility dysfunction in patients with irritable bowel syndrome.

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Section: Discussionmentioning

confidence: 51%

Norepinephrine mediates the transcriptional effects of heterotypic chronic stress on colonic motor function

Choudhury¹,

Shi²,

Sarna³

2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…These findings have two relevant considerations. First, drainage from the CNS to the cervical lymph nodes has been associated with modulation of neuroimmune events (Cserr and Knopf, 1992;Knopf et al, 1995) and uptake from brain to blood of peptides can modulate splenic function (Martins et al, 1997). Our findings show that each of the three routes would produce a very different profile of neuroimmune versus peripheral immune activation.…”

Section: Discussionmentioning

confidence: 80%

Delivery of Galanin-Like Peptide to the Brain: Targeting with Intranasal Delivery and Cyclodextrins

Nonaka

Farr

Kageyama

et al. 2008

J Pharmacol Exp Ther

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“…injection, although only a single high dose (400 g/kg) was tested in this study (Asakawa et al, 1999). The long-lasting effect of r/hCRF may be related to its halflife, which was estimated to be 151 min from elimination kinetics studies in mice (Martins et al, 1997). Likewise, CRF induces a long-lasting and dose-dependent inhibition of gastric emptying of a non-nutrient liquid solution when administered i.p.…”

Section: Discussionmentioning

confidence: 99%

Differential Actions of Peripheral Corticotropin-Releasing Factor (CRF), Urocortin II, and Urocortin III on Gastric Emptying and Colonic Transit in Mice: Role of CRF Receptor Subtypes 1 and 2

Martı́nez

Wang²,

Rivier³

et al. 2002

J Pharmacol Exp Ther

162

194

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Peripheral CRF inhibits gastric emptying and stimulates colonic motor function in rats. We investigated the role of CRF 1 and CRF 2 receptors in i.p. CRF-induced alterations of gut transit in conscious mice using selective CRF 1 and CRF 2 ligands injected i.p. Gastric emptying 2 h after ingestion of a solid chow meal and colonic transit (time to expel a bead inserted into the distal colon) were determined simultaneously. Rat/human (r/ h)CRF, which has CRF 1 Ͼ CRF 2 binding affinity, decreased distal colonic transit time at lower doses (6 -12 g/kg) than those inhibiting gastric emptying (20 -60 g/kg). Ovine CRF, a preferential CRF 1 receptor agonist (6 -60 g/kg), reduced significantly the colonic transit time without altering gastric emptying, whereas the selective CRF 2 receptor agonists mouse urocortin II (20 -60 g/kg) and urocortin III (120 g/kg) inhibited significantly gastric emptying without modifying colonic transit. The CRF 1 /CRF 2 receptor antagonist, astressin (30 -120 g/kg), , dose dependently abolished r/hCRF-induced delayed gastric emptying and had no effect on colonic response. These data show that i.p. r/hCRF-induced opposite actions on upper and lower gut transit in conscious mice are mediated by different CRF receptor subtypes: the activation of CRF 1 receptors stimulates colonic propulsive activity, whereas activation of CRF 2 receptors inhibits gastric emptying.

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Transport of CRH from mouse brain directly affects peripheral production of β-endorphin by the spleen

Cited by 24 publications

References 34 publications

Norepinephrine mediates the transcriptional effects of heterotypic chronic stress on colonic motor function

Norepinephrine mediates the transcriptional effects of heterotypic chronic stress on colonic motor function

Delivery of Galanin-Like Peptide to the Brain: Targeting with Intranasal Delivery and Cyclodextrins

Differential Actions of Peripheral Corticotropin-Releasing Factor (CRF), Urocortin II, and Urocortin III on Gastric Emptying and Colonic Transit in Mice: Role of CRF Receptor Subtypes 1 and 2

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