Altered adrenal chromaffin cell function during experimental colitis

Lukewich, Mark K.; Lomax, Alan E.

doi:10.1152/ajpgi.00298.2010

Cited by 7 publications

(14 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No significant difference in the amplitude of I Ca generated in response to square pulse depolarizations or AP waveforms was observed between groups. LPS also did not alter intracellular [Ca 2ϩ ] dynamics during high-K ϩ -induced depolarizations (data not shown), as assessed using Ca 2ϩ imaging techniques (5).…”

Section: Fig 2 Acc Excitability Is Reduced By Lps Current Clamp Rementioning

confidence: 86%

“…Delayed rectifier voltagegated K ϩ currents (I K ) were measured during the last 100 msec of each 500-msec stimulus waveform, as previously described (5). For experiments assessing Ca 2ϩ -activated K ϩ channels, apamin (500 nM) or iberiotoxin (50 nM; Tocris Bioscience, Minneapolis, MN) was bath applied for 5 min to inhibit small-conductance (SK) or large-conductance (BK) Ca 2ϩ -activated K ϩ channels, respectively (22,23).…”

Section: Electrophysiologymentioning

confidence: 99%

“…Pathological inflammatory conditions that promote bacterial translocation into the circulation have been associated with changes in ACC function (5)(6)(7). Although…”

Section: Potential Significancementioning

confidence: 99%

“…Although it is well established that inflammatory mediators can modulate the electrophysiological properties and neurochemistry of ACCs (2)(3)(4), it is less clear what effect, if any, microbial antigens have on ACC function. This is an important issue, because several diseases associated with bacterial translocation into the circulation, including sepsis and inflammatory bowel disease (IBD), alter the function of ACCs (5)(6)(7). It is possible that direct effects of microbial products on ACCs account for some of these changes.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Toll-Like Receptor 4 Activation Reduces Adrenal Chromaffin Cell Excitability Through a Nuclear Factor-κB-Dependent Pathway

Lukewich

Lomax

2013

Endocrinology

Self Cite

View full text Add to dashboard Cite

The adrenal medulla contains fenestrated capillaries that allow catecholamines and neuropeptides secreted by adrenal chromaffin cells (ACCs) to readily access the circulation. These capillaries may also allow bacterial products to enter the adrenal medulla and interact with ACCs during infection. One potential mediator of this interaction is toll-like receptor 4 (TLR-4), a pattern-recognition receptor that detects lipopolysaccharide (LPS) from Gram-negative bacteria. Evidence suggests that excitable cells can express TLR-4 and that LPS can modulate important neuronal and endocrine functions. The present study was therefore performed to test the hypothesis that TLR-4 activation by LPS affects ACC excitability and secretory output. RT-PCR revealed that TLR-4, cluster of differentiation 14, myeloid differentiation protein-2, and myeloid-derived factor 88 are expressed within mouse adrenal medullae. TLR-4 immunoreactivity was observed within all tyrosine hydroxylase immunoreactive ACCs. Incubation of isolated ACCs in LPS dose dependently hyperpolarized the resting membrane potential and enhanced large conductance (BK) Ca(2+)-activated K(+) currents. LPS (10 μg/ml) also increased rheobase, decreased the number of action potentials fired at rheobase, and reduced the percentage of ACCs exhibiting spontaneous and anodal break action potentials. Although catecholamine release was unaltered, LPS significantly reduced high-K(+)-stimulated neuropeptide Y release from isolated ACCs. LPS did not alter the excitability of ACCs from TLR-4(-/-) mice. Inhibition of nuclear factor-κB signaling with SC-514 (20 μm) abolished the effects of LPS on ACC excitability. Our findings suggest that LPS acts at TLR-4 to reduce ACC excitability and neuropeptide Y release through an nuclear factor-κB-dependent pathway.

show abstract

Section: Fig 2 Acc Excitability Is Reduced By Lps Current Clamp Rementioning

confidence: 86%

Section: Electrophysiologymentioning

confidence: 99%

“…Pathological inflammatory conditions that promote bacterial translocation into the circulation have been associated with changes in ACC function (5)(6)(7). Although…”

Section: Potential Significancementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Toll-Like Receptor 4 Activation Reduces Adrenal Chromaffin Cell Excitability Through a Nuclear Factor-κB-Dependent Pathway

Lukewich

Lomax

2013

Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The procedure used to isolate mouse ACCs was adapted from Kolski-Andreaco et al (2007) (34) and is described in detail by Lukewich and Lomax (2011) (35). Mice were deeply anesthetized using isofluorane inhalation and euthanized by cervical dislocation.…”

Section: Isolation Of Adrenal Chromaffin Cellsmentioning

confidence: 99%

Endotoxemia Enhances Catecholamine Secretion From Male Mouse Adrenal Chromaffin Cells Through an Increase In Ca2+ Release From the Endoplasmic Reticulum

Lukewich

Lomax

2014

Endocrinology

Self Cite

View full text Add to dashboard Cite

Enhanced epinephrine secretion from adrenal chromaffin cells (ACCs) is an important homeostatic response to severe systemic inflammation during sepsis. Evidence suggests that increased activation of ACCs by preganglionic sympathetic neurons and direct alterations in ACC function contribute to this response. However, the direct effects of sepsis on ACC function have yet to be characterized. We hypothesized that sepsis enhances epinephrine secretion from ACCs by increasing intracellular Ca(2+) signaling. Plasma epinephrine concentration was increased 5-fold in the lipopolysaccharide-induced endotoxemia model of sepsis compared with saline-treated control mice. Endotoxemia significantly enhanced stimulus-evoked epinephrine secretion from isolated ACCs in vitro. Carbon fiber amperometry revealed an increase in the number of secretory events during endotoxemia, without significant changes in spike amplitude, half-width, or quantal content. ACCs isolated up to 12 hours after the induction of endotoxemia exhibited larger stimulus-evoked Ca(2+) transients compared with controls. Similarly, ACCs from cecal ligation and puncture mice also exhibited enhanced Ca(2+) signaling. Although sepsis did not significantly affect ACC excitability or voltage-gated Ca(2+) currents, a 2-fold increase in caffeine (10 mM)-stimulated Ca(2+) transients was observed during endotoxemia. Depletion of endoplasmic reticulum Ca(2+) stores using cyclopiazonic acid (10 μM) abolished the effects of endotoxemia on catecholamine secretion from ACCs. These findings suggest that sepsis directly enhances catecholamine secretion from ACCs through an increase in Ca(2+) release from the endoplasmic reticulum. These alterations in ACC function are likely to amplify the effects of increased preganglionic sympathetic neuron activity to further enhance epinephrine levels during sepsis.

show abstract

Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis

Benson

Moynes

et al. 2014

Cell Tissue Res

View full text Add to dashboard Cite

Sensitization of dorsal root ganglia (DRG) neurons is an important mechanism underlying the expression of chronic abdominal pain caused by intestinal inflammation. Most studies have focused on changes in the peripheral terminals of DRG neurons in the inflamed intestine but recent evidence suggests that the sprouting of central nerve terminals in the dorsal horn is also important. Therefore, we examine the time course and reversibility of changes in the distribution of immunoreactivity for substance P (SP), a marker of the central terminals of DRG neurons, in the spinal cord during and following dextran sulphate sodium (DSS)-induced colitis in mice. Acute and chronic treatment with DSS significantly increased SP immunoreactivity in thoracic and lumbosacral spinal cord segments. This increase developed over several weeks and was evident in both the superficial laminae of the dorsal horn and in lamina X. These increases persisted for 5 weeks following cessation of both the acute and chronic models. The increase in SP immunoreactivity was not observed in segments of the cervical spinal cord, which were not innervated by the axons of colonic afferent neurons. DRG neurons dissociated following acute DSS-colitis exhibited increased neurite sprouting compared with neurons dissociated from control mice. These data suggest significant colitis-induced enhancements in neuropeptide expression in DRG neuron central terminals. Such neurotransmitter plasticity persists beyond the period of active inflammation and might contribute to a sustained increase in nociceptive signaling following the resolution of inflammation.

show abstract

Altered adrenal chromaffin cell function during experimental colitis

Abstract: Lukewich MK, Lomax AE. Altered adrenal chromaffin cell function during experimental colitis.

Cited by 7 publications

References 63 publications

Toll-Like Receptor 4 Activation Reduces Adrenal Chromaffin Cell Excitability Through a Nuclear Factor-κB-Dependent Pathway

Toll-Like Receptor 4 Activation Reduces Adrenal Chromaffin Cell Excitability Through a Nuclear Factor-κB-Dependent Pathway

Endotoxemia Enhances Catecholamine Secretion From Male Mouse Adrenal Chromaffin Cells Through an Increase In Ca2+ Release From the Endoplasmic Reticulum

Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis

Contact Info

Product

Resources

About