Chromaffin cell action potentials and their possible role in adrenaline secretion from rat adrenal medulla.

OBJECTIVE: To study survivin expression in human adrenal medulla and in benign and malignant pheochromocytoma tissue as a tool to predict tumor metastatic potential and prognosis. DESIGN: Blinded study to assess the role of the anti-survivin antibody in chromaffin cells. METHODS: We performed immunohistochemistry with a purified rabbit-polyclonal anti-survivin antibody on 39 formalin-fixed and paraffin-embedded pheochromocytoma/paraganglioma specimens, and on 10 normal adrenal medulla samples from patients unaffected by a chromaffin cell tumor. Fourteen samples were from 14 patients with benign pheochromocytoma (<8 year follow-up, mean 5.2 years), 18 specimens were from 12 patients with malignant pheochromocytoma (<13 year follow-up, mean 6.3 years), 5 samples were from 2 patients with malignant paraganglioma (<6 year follow-up, mean 4 years), and 2 specimens from 2 patients with benign paraganglioma (<7 year follow-up, mean 5.5 years). Malignancy was defined by metastases in non-chromaffin tissues. Staining intensity with the anti-survivin antibody was scored from 0 (none) to 3+ (heavy). Tissues from human kidney, breast, and melanoma served as controls. RESULTS: All pheochromocytoma/paraganglioma specimens stained either 2+ or 3+. By analysis of variance (ANOVA), there was no statistically significant difference between the staining intensity of benign and malignant samples. All normal adrenal medulla specimens stained positively with anti-survivin but to a lesser degree than the chromaffin cell tumors (P<0.01). CONCLUSIONS: Based on these findings, we conclude that (i) survivin may represent a novel neuroendocrine marker for chromaffin cell tumors, and (ii) survivin does not appear to reliably distinguish benign from malignant pheochromocytomas/paragangliomas and thus does not identify patients at risk of recurrent disease.

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Non-Chromaffin Cell Constituents of the Adrenal Medulla are Detrimental to the Survival of Grafted Adrenal Chromaffin Cells: Studies in Rats and Non-Human Primates

Journal of Neural Transplantation and Plasticity ◽

10.1155/np.1992.209 ◽

1992 ◽

Vol 3 (4) ◽

pp. 209-210 ◽

Cited By ~ 1

Author(s):

Sherry B. Schueler ◽

John D. Ortega ◽

Jacqueline Sagen ◽

Jeffrey H. Kordower

Keyword(s):

Adrenal Medulla ◽

Chromaffin Cells ◽

Chromaffin Cell ◽

Adrenal Chromaffin Cells ◽

Adrenal Chromaffin

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Comparative Studies of Chromaffin Cell Proliferation in the Adrenal Medulla of Rats and Mice

Toxicological Sciences ◽

10.1093/toxsci/35.2.216 ◽

1997 ◽

Vol 35 (2) ◽

pp. 216-220

Author(s):

ARTHUR S. TISCHLER ◽

JAMES F. POWERS ◽

MEHZAD SHAHSAVARI ◽

JEFFREY ZIAR ◽

PANAYIOTIS TSOKAS ◽

...

Keyword(s):

Cell Proliferation ◽

Adrenal Medulla ◽

Comparative Studies ◽

Chromaffin Cell ◽

Rats And Mice

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Vitamin D3, Lactose, and Xylitol Stimulate Chromaffin Cell Proliferation in the Rat Adrenal Medulla

Toxicology and Applied Pharmacology ◽

10.1006/taap.1996.0204 ◽

1996 ◽

Vol 140 (1) ◽

pp. 115-123 ◽

Cited By ~ 23

Author(s):

Arthur S. Tischler ◽

James F. Powers ◽

John C. Downing ◽

Jocelyn C. Riseberg ◽

Mehzad Shahsavari ◽

...

Keyword(s):

Cell Proliferation ◽

Adrenal Medulla ◽

Vitamin D3 ◽

Chromaffin Cell

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Electrical activity in chromaffin cells of intact mouse adrenal gland

AJP Cell Physiology ◽

10.1152/ajpcell.1988.254.5.c675 ◽

1988 ◽

Vol 254 (5) ◽

pp. C675-C683 ◽

Cited By ~ 43

Author(s):

V. Nassar-Gentina ◽

H. B. Pollard ◽

E. Rojas

Keyword(s):

Cell Membrane ◽

Adrenal Gland ◽

Electrical Activity ◽

Action Potentials ◽

Chromaffin Cells ◽

Chromaffin Cell ◽

Resting Potential ◽

Constant Field ◽

Intact Mouse

Membrane potentials of medullary chromaffin cells of the adrenal gland of the mouse were measured in situ. Resting potential (-54.3 +/- 8.8 mV) depended on extracellular [K+] as predicted by the constant-field equation with a permeability ratio, PNa/PK, of 0.09. Current-voltage (I-V) relationships showed that the current is rectified across the chromaffin cell membrane. A rectification ratio of 0.4 was calculated from the slopes of the I-V curves for positive (41 +/- 26 M omega) and negative (103 +/- M omega) currents. Because input resistance for a resting chromaffin cell in isolation is approximately 5 G omega, the chromaffin cells in situ behave as if they were electrically coupled. Most cells responded to depolarizing current pulses with repetitive action potentials, but only 50% of them showed spontaneous electrical activity. Spontaneous activity was often seen in the presence of tetrodotoxin (3 microM). Although the application of the K+-channel blockers tetraethylammonium and Ba2+ greatly increased the amplitude of the action potentials, only Ba2+ induced continuous electrical activity. Application of acetylcholine (ACh) always depolarized the cell membrane. This effect was blocked by atropine but not by D-tubocurarine, suggesting that ACh stimulation of chromaffin cells in the mouse involves activation of muscarinic receptors.

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Cell adhesion molecules (CAMs) in adrenal medulla in situ and in vitro: Enhancement of chromaffin cell L1Ng-CAM expression by NGF

Experimental Neurology ◽

10.1016/0014-4886(90)90051-s ◽

1990 ◽

Vol 110 (1) ◽

pp. 52-72 ◽

Cited By ~ 20

Author(s):

Maciej Poltorak ◽

Kotaro Shimoda ◽

William J. Freed

Keyword(s):

Cell Adhesion ◽

Adhesion Molecules ◽

Adrenal Medulla ◽

Cell Adhesion Molecules ◽

Chromaffin Cell

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NGF-like trophic support from peripheral nerve for grafted rhesus adrenal chromaffin cells

Journal of Neurosurgery ◽

10.3171/jns.1990.73.3.0418 ◽

1990 ◽

Vol 73 (3) ◽

pp. 418-428 ◽

Cited By ~ 126

Author(s):

Jeffrey H. Kordower ◽

Massimo S. Fiandaca ◽

Mary F. D. Notter ◽

John T. Hansen ◽

Don M. Gash

Keyword(s):

Tyrosine Hydroxylase ◽

Adrenal Medulla ◽

Sural Nerve ◽

Chromogranin A ◽

Chromaffin Cells ◽

Chromaffin Cell ◽

Adrenal Chromaffin Cells ◽

Content Type ◽

Adrenal Chromaffin ◽

Fine Print

✓ Autopsy results on patients and corresponding studies in nonhuman primates have revealed that autografts of adrenal medulla into the striatum, used as a treatment for Parkinson's disease, do not survive well. Because adrenal chromaffin cell viability may be limited by the low levels of available nerve growth factor (NGF) in the striatum, the present study was conducted to determine if transected peripheral nerve segments could provide sufficient levels of NGF to enhance chromaffin cell survival in vitro and in vivo. Aged female rhesus monkeys, rendered hemiparkinsonian by the drug MPTP (n-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), received autografts into the striatum using a stereotactic approach, of either sural nerve or adrenal medulla, or cografts of adrenal medulla and sural nerve (three animals in each group). Cell cultures were established from tissue not used in the grafts. Adrenal chromaffin cells either cocultured with sural nerve segments or exposed to exogenous NGF differentiated into a neuronal phenotype. Chromaffin cell survival, when cografted with sural nerve into the striatum, was enhanced four- to eightfold from between 8000 and 18,000 surviving cells in grafts of adrenal tissue only up to 67,000 surviving chromaffin cells in cografts. In grafts of adrenal tissue only, the implant site consisted of an inflammatory focus. Surviving chromaffin cells, which could be identified by both chromogranin A and tyrosine hydroxylase staining, retained their endocrine phenotype. Cografted chromaffin cells exhibited multipolar neuritic processes and numerous chromaffin granules, and were also immunoreactive for tyrosine hydroxylase and chromogranin A. Blood vessels within the graft were fenestrated, indicating that the blood-brain barrier was not intact. Additionally, cografted chromaffin cells were observed in a postsynaptic relationship with axon terminals from an undetermined but presumably a host origin.

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

Endocrinology ◽

10.1210/en.2012-1534 ◽

2013 ◽

Vol 154 (1) ◽

pp. 351-362 ◽

Cited By ~ 10

Author(s):

Mark K. Lukewich ◽

Alan E. Lomax

Keyword(s):

Neuropeptide Y ◽

Adrenal Medulla ◽

Action Potentials ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Neuropeptide Y Release ◽

Adrenal Chromaffin ◽

Dependent Pathway

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) Ca2+-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.

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Chromaffin cell survival and host dopaminergic fiber recovery in a patient with Parkinson's disease treated by cografts of adrenal medulla and pretransected peripheral nerve

Journal of Neurosurgery ◽

10.3171/jns.1996.84.4.0685 ◽

1996 ◽

Vol 84 (4) ◽

pp. 685-689 ◽

Cited By ~ 32

Author(s):

Isao Date ◽

Takashi Imaoka ◽

Yasuyuki Miyoshi ◽

Takeshi Ono ◽

Shoji Asari ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Peripheral Nerve ◽

Adrenal Medulla ◽

Chromaffin Cells ◽

Chromaffin Cell ◽

Caudate Nuclei ◽

Modest Improvement ◽

Content Type ◽

Grafting Procedure

✓ A 55-year-old woman with severe Parkinson's disease was treated by cografting adrenal medulla with pretransected peripheral nerve into the bilateral caudate nuclei. The patient showed modest improvement of her akinesia; this effect persisted for 1 year after transplantation, when she suddenly died from upper gastrointestinal bleeding unrelated to the grafting procedure. At autopsy, a large number of tyrosine hydroxylase—immunoreactive chromaffin cells were observed within the caudate graft sites and a dense network of host dopaminergic fibers was visualized. This autopsy finding is very important for the field of experimental and clinical chromaffin cell grafting because it is the first evidence that cografts using pretransected peripheral nerve might enhance the survival of chromaffin cells and the recovery of host dopaminergic fibers in humans suffering from Parkinson's disease.

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