Dual Action of GABA&lt;sub&gt;A&lt;/sub&gt; Receptors on the Secretory Process of Melanotrophs of &lt;i&gt;Xenopus laevis&lt;/i&gt;

Jenks, Bruce G.; Koning, Harry P. de; Valentijn, Karine M.; Roubos, Eric W.

doi:10.1159/000126516

Cited by 8 publications

(12 citation statements)

References 14 publications

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“…We were interested by reports pointing to a chloride channel‐dependent component of the neuroendocrine circuit. In particular, that picrotoxin (100 μM) induces α ‐MSH secretion from cultured adult frog melanotropes (Desrues et al., ; Jenks et al., ; Louiset et al., ), and Xenopus embryos treated for a few days during early development with ivermectin become darkly pigmented via a reported morphological colour response (Blackiston et al., ). The in vivo effects of these chloride channels modulators in physiological skin changes are unknown.…”

Section: Resultsmentioning

confidence: 99%

“…In support, axonal fibres that contact melanotropes contain the inhibitory neuropeptides neuropeptide Y, dopamine and γ ‐aminobutyric acid (GABA) (Tuinhof et al., ; Ubink et al., ). GABA, through chloride‐dependent calcium release, inhibits α ‐MSH secretion from cultured adult rat and frog melanotropes (Desrues et al., ; Tomiko et al., ; Verburg‐Van Kemenade et al., ), which can be blocked by a GABA A receptor (GABA A R) antagonist, picrotoxin (Figure A) (Desrues et al., ; Jenks et al., ; Louiset et al., ; Verburg‐van Kemenade et al., ; Zhang et al., ). Whether a picrotoxin‐sensitive GABA‐mediated mechanism functions in vivo to regulate α ‐MSH and skin pigmentation is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological induction of skin pigmentation unveils the neuroendocrine circuit regulated by light

Bertolesi

Vazhappilly

Hehr

et al. 2016

Pigment Cell Melanoma Res

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Light-regulated skin colour change is an important physiological process in invertebrates and lower vertebrates, and includes daily circadian variation and camouflage (i.e. background adaptation). The photoactivation of melanopsin-expressing retinal ganglion cells (mRGCs) in the eye initiates an uncharacterized neuroendocrine circuit that regulates melanin dispersion/aggregation through the secretion of alpha-melanocyte-stimulating hormone (α-MSH). We developed experimental models of normal or enucleated Xenopus embryos, as well as in situ cultures of skin of isolated dorsal head and tails, to analyse pharmacological induction of skin pigmentation and α-MSH synthesis. Both processes are triggered by a melanopsin inhibitor, AA92593, as well as chloride channel modulators. The AA9253 effect is eye-dependent, while functional data in vivo point to GABAA receptors expressed on pituitary melanotrope cells as the chloride channel blocker target. Based on the pharmacological data, we suggest a neuroendocrine circuit linking mRGCs with α-MSH secretion, which is used normally during background adaptation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacological induction of skin pigmentation unveils the neuroendocrine circuit regulated by light

Bertolesi

Vazhappilly

Hehr

et al. 2016

Pigment Cell Melanoma Res

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“…MELANOTROPE CELL When the actions of DA, GABA and NPY on ␣-MSH release (occurring within minutes; Leenders et al, 1993) and on POMC biosynthesis (occurring after hours to days; Dotman et al, 1996Dotman et al, , 1998aMartens et al, 1987) are compared, it appears that each factor has its own, specific inhibitory action. So, stimulation of either the GABA A -receptor or GABA B -receptor leads to a strong short-term but only a moderate long-term inhibition (Buzzi et al, 1997;Jenks et al, 1993b). Stimulation of the dopamine D2-like receptor results in a strong, short-term as well as a strong, long-term inhibition.…”

Section: Multiple Control Of Thementioning

confidence: 99%

Dynamics and plasticity of peptidergic control centres in the retino‐brain‐pituitary system of Xenopus laevis

Krämer

Kolk

Berghs

et al. 2001

Microscopy Res & Technique

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This review deals particularly with the recent literature on the structural and functional aspects of the retino-brain-pituitary system that controls the physiological process of background adaptation in the aquatic toad Xenopus laevis. Taking together the large amount of multidisciplinary data, a consistent picture emerges of a highly plastic system that efficiently responds to changes in the environmental light condition by releasing POMC-derived peptides, such as the peptide alpha-melanophore-stimulating hormone (alpha-MSH), into the circulation. This plasticity is exhibited by both the central nervous system and the pituitary pars intermedia, at the level of molecules, subcellular structures, synapses, and cells. Signal transduction in the pars intermedia of the pituitary gland of Xenopus laevis appears to be a complex event, involving various environmental factors (e.g., light and temperature) that act via distinct brain centres and neuronal messengers converging on the melanotrope cells. In the melanotropes, these messages are translated by specific receptors and second messenger systems, in particular via Ca(2+) oscillations, controlling main secretory events such as gene transcription, POMC-precursor translation and processing, posttranslational peptide modifications, and release of a bouquet of POMC-derived peptides. In conclusion, the Xenopus hypothalamo-hypophyseal system involved in background adaptation reveals how neuronal plasticity at the molecular, cellular and organismal levels, enable an organism to respond adequately to the continuously changing environmental factors demanding physiological adaptation.

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“…On a black back-ground, the melanotrope cell is dedicated to produce vast amounts of POMC such that this prohormone represents ϳ80% of all newly synthesized melanotrope proteins. On a white background, POMC mRNA levels are decreased ϳ30-fold (Holthuis et al, 1995a) and ␣-MSH secretion from the melanotropes into the bloodstream is inhibited by neurons of hypothalamic origin that directly innervate the cells (Jenks et al, 1993;Tuinhof et al, 1994), leading to melanosome aggregation and, consequently, pallor of the skin. Placing Xenopus on a black or a white background therefore allows physiological manipulation of the biosynthetic and secretory activities of the melanotrope cell.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, deletion of all p24 proteins resulted in viable yeast (Marzioch et al, 1999;Springer et al, 2000), whereas genetic ablation of a single p24 family member caused early lethality in mice (Denzel et al, 2000). To investigate the significance of the p24 system in a highly specialized secretory cell, we decided to use a physiological model (background adaptation of the South-African clawed frog, Xenopus laevis) with a well-defined secretory cell (the intermediate pituitary melanotrope cell) and its single major soluble cargo protein proopiomelanocortin (POMC) (Roubos, 1997 et al, 1995a) and ␣-MSH secretion from the melanotropes into the bloodstream is inhibited by neurons of hypothalamic origin that directly innervate the cells (Jenks et al, 1993;Tuinhof et al, 1994), leading to melanosome aggregation and, consequently, pallor of the skin. Placing Xenopus on a black or a white background therefore allows physiological manipulation of the biosynthetic and secretory activities of the melanotrope cell.…”

mentioning

confidence: 99%

A Cell-Specific Transgenic Approach inXenopusReveals the Importance of a Functional p24 System for a Secretory Cell

Bouw¹,

Huizen²,

Jansen³

et al. 2004

MBoC

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The p24␣, -␤, -␥, and -␦ proteins are major multimeric constituents of cycling endoplasmic reticulum-Golgi transport vesicles and are thought to be involved in protein transport through the early secretory pathway. In this study, we targeted transgene overexpression of p24␦ 2 specifically to the Xenopus intermediate pituitary melanotrope cell that is involved in background adaptation of the animal and produces high levels of its major secretory cargo proopiomelanocortin (POMC). The transgene product effectively displaced the endogenous p24 proteins, resulting in a melanotrope cell p24 system that consisted predominantly of the transgene p24␦ 2 protein. Despite the severely distorted p24 machinery, the subcellular structures as well as the level of POMC synthesis were normal in these cells. However, the number and pigment content of skin melanophores were reduced, impairing the ability of the transgenic animal to fully adapt to a black background. This physiological effect was likely caused by the affected profile of POMC-derived peptides observed in the transgenic melanotrope cells. Together, our results suggest that in the early secretory pathway an intact p24 system is essential for efficient secretory cargo transport or for supplying cargo carriers with the correct protein machinery to allow proper secretory protein processing. INTRODUCTIONTransport of cargo proteins through the early secretory pathway involves cargo selection, transport vesicle formation, quality control to recycle misfolded cargo, and cycling of the COPI-and COPII-coated vesicles between the endoplasmic reticulum (ER) and Golgi (Barlowe, 2000). One of the major constituents of the transport vesicles is the p24 family of type I transmembrane proteins that can be classified into four main subfamilies, designated p24␣, -␤, -␥, and -␦ (Schimmö ller et al., 1995;Stamnes et al., 1995;Sohn et al., 1996;Nickel et al., 1997;Dominguez et al., 1998). The p24 proteins share a number of structural characteristics, such as a relatively large lumenal putative cargo-binding domain, a coiled-coil region thought to be involved in the formation of multimeric p24 complexes, a transmembrane region, and a short cytoplasmic tail containing COPI-and COPII-binding motifs that are used for p24 traveling from the ER to the Golgi and back (for review, see Kaiser, 2000). In yeast and mammalian cells, p24 proteins form functional heterotetrameric complexes containing one representative of each subfamily, whereby the composition of the complex may differ in various cell types (Dominguez et al., 1998;Fü llekrug et al., 1999;Marzioch et al., 1999;Ciufo and Boyd, 2000;Emery et al., 2000;Belden and Barlowe, 2001). Furthermore, the stability of the p24 members seems to be compromised when cells are deficient in the expression of a single p24 protein (Marzioch et al., 1999;Denzel et al., 2000). Recent evidence suggests a complex and dynamic p24 system of mostly monomers and homo-/heterodimers and that the degree of oligomerization constantly alters and largely depends on the s...

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Dual Action of GABA<sub>A</sub> Receptors on the Secretory Process of Melanotrophs of <i>Xenopus laevis</i>

Cited by 8 publications

References 14 publications

Pharmacological induction of skin pigmentation unveils the neuroendocrine circuit regulated by light

Pharmacological induction of skin pigmentation unveils the neuroendocrine circuit regulated by light

Dynamics and plasticity of peptidergic control centres in the retino‐brain‐pituitary system of Xenopus laevis

A Cell-Specific Transgenic Approach inXenopusReveals the Importance of a Functional p24 System for a Secretory Cell

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