Nicotinic acetylcholine receptors regulate type 1 inositol 1,4,5-trisphosphate receptor expression via calmodulin kinase IV activation

Among the neurotoxicants contained in tobacco smoke, if absorbed during pregnancy, nicotine significantly affects α7-nicotinic acetylcholine receptors, which play essential roles in the development of the brainstem regions receiving cholinergic projections in perinatal life. Immunohistochemical procedures for analysing formalin-fixed and paraffin-embedded brainstem samples from 68 fetuses and early newborns, with smoking and non-smoking mothers, who died of known and unknown causes, were carried out in order to determine if nicotine had activated the α7-nicotinic acetylcholine receptors. High α7-nicotinic acetylcholine receptor expression levels were only observed in the victims with smoking mothers. Frequently, these findings were associated with the hypoplasia of the brainstem structures controlling vital functions. The results of this study indicate that the exposition to nicotine in pregnancy exerts a strong direct effect on α7-nicotinic acetylcholine receptor activity especially in perinatal life and may be one of the primary risk factors leading to the sudden unexplained death of fetuses and newborns.

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Dopamine D1 receptors regulate type 1 inositol 1,4,5-trisphosphate receptor expression via both AP-1- and NFATc4-mediated transcriptional processes

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2012.07827.x ◽

2012 ◽

Vol 122 (4) ◽

pp. 702-713 ◽

Cited By ~ 15

Author(s):

Koji Mizuno ◽

Kazuhiro Kurokawa ◽

Seitaro Ohkuma

Keyword(s):

Receptor Expression ◽

D1 Receptors ◽

Dopamine D1 Receptors ◽

Inositol 1,4,5 Trisphosphate ◽

Trisphosphate Receptor

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Amacrine, ganglion, and displaced amacrine cells in the rabbit retina express nicotinic acetylcholine receptors

Visual Neuroscience ◽

10.1017/s095252380017508x ◽

2000 ◽

Vol 17 (5) ◽

pp. 743-752 ◽

Cited By ~ 46

Author(s):

KENT T. KEYSER ◽

MARGARET A. MACNEIL ◽

NINA DMITRIEVA ◽

FAN WANG ◽

RICHARD H. MASLAND ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Ganglion Cells ◽

Plexiform Layer ◽

Amacrine Cells ◽

Receptor Expression ◽

Inner Plexiform Layer ◽

Rabbit Retina ◽

Nicotinic Acetylcholine ◽

Starburst Amacrine Cells

Acetylcholine (ACh) in the vertebrate retina affects the response properties of many ganglion cells, including those that display directional selectivity. Three β and eight α subunits of neuronal nicotinic acetylcholine receptors (nAChRs) have been purified and antibodies have been raised against many of them. Here we describe biochemical and immunocytochemical studies of nAChRs in the rabbit retina. Radioimmunoassay and Western blot analysis demonstrated that many of the nAChRs recognized by a monoclonal antibody (mAb210) contain β2 subunits, some of which are in combination with α3 and possibly other subunits. MAb210-immunoreactive cells in the inner nuclear layer (INL) were 7–14 μm in diameter and were restricted to the innermost one or two tiers of cells, although occasional cells were found in the middle of the INL. At least 60% of the cells in the ganglion cell layer (GCL) in the visual streak displayed mAb210 immunoreactivity; these neurons ranged from 7–18 μm in diameter. The dendrites of cells in both the INL and GCL could sometimes be followed until they entered one of two dense, poorly defined, bands of processes in the inner plexiform layer (IPL) that overlap the arbors of the cholinergic starburst cells. Parvalbumin and serotonin-positive neurons did not exhibit nAChR immunoreactivity. Although the level of receptor expression appeared to be low, mAb210 immunoreactivity was observed in some of the ChAT-positive (starburst) amacrine cells.

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Bcl-2 overexpression prevents calcium overload and subsequent apoptosis in dystrophic myotubes

Biochemical Journal ◽

10.1042/bj20051265 ◽

2006 ◽

Vol 395 (2) ◽

pp. 267-276 ◽

Cited By ~ 41

Author(s):

Olivier Basset ◽

François-Xavier Boittin ◽

Christian Cognard ◽

Bruno Constantin ◽

Urs T. Ruegg

Keyword(s):

Plasma Membrane ◽

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Calcium Overload ◽

Mdx Mice ◽

Mitochondrial Calcium ◽

Protein Overexpression ◽

Nicotinic Acetylcholine ◽

Calcium Dependent ◽

Inositol 1,4,5 Trisphosphate

Duchenne muscular dystrophy (DMD) is a lethal disease caused by the lack of the cytoskeletal protein dystrophin. Altered calcium homoeostasis and increased calcium concentrations in dystrophic fibres may be responsible for the degeneration of muscle occurring in DMD. In the present study, we used subsarcolemmal- and mitochondrial-targeted aequorin to study the effect of the antiapoptotic Bcl-2 protein overexpression on carbachol-induced near-plasma membrane and mitochondrial calcium responses in myotubes derived from control C57 and dystrophic (mdx) mice. We show that Bcl-2 overexpression decreases subsarcolemmal and mitochondrial calcium overload that occurs during activation of nicotinic acetylcholine receptors in dystrophic myotubes. Moreover, our results suggest that overexpressed Bcl-2 protein may prevent near-plasma membrane and mitochondrial calcium overload by inhibiting IP3Rs (inositol 1,4,5-trisphosphate receptors), which we have shown previously to be involved in abnormal calcium homoeostasis in dystrophic myotubes. Most likely as a consequence, the inhibition of IP3R function by Bcl-2 also inhibits calcium-dependent apoptosis in these cells.

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Nicotinic acetylcholine receptor expression by directionally selective ganglion cells

Visual Neuroscience ◽

10.1017/s0952523807070435 ◽

2007 ◽

Vol 24 (4) ◽

pp. 523-533 ◽

Cited By ~ 11

Author(s):

CHRISTIANNE E. STRANG ◽

JORDAN M. RENNA ◽

FRANKLIN R. AMTHOR ◽

KENT T. KEYSER

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Ganglion Cells ◽

Partial Agonist ◽

Receptor Expression ◽

Nicotinic Acetylcholine ◽

Preferred Direction ◽

Α7 Nachr ◽

Bath Application ◽

Α7 Nachrs

Acetylcholine (ACh) enhances the preferred direction responses of directionally selective ganglion cells (DS GCs; Ariel & Daw, 1982; Ariel & Adolph, 1985) through the activation of nicotinic acetylcholine receptors (nAChRs; Ariel & Daw, 1982; Massey et al., 1997; Kittila & Massey, 1997). DS GCs appear to express at least two types of nAChRs, those that are sensitive to the partially subtype-specific antagonist methyllycaconitine (MLA), and those that are MLA-insensitive (Reed et al., 2002). Our purpose was to confirm the expression of α7 nAChRs by DS GCs and to assess the contributions of other nAChR subtypes to DS GC responses. Using choline as a nAChR partially subtype-specific agonist, we found that the majority of DS GCs demonstrated responses to choline while under synaptic blockade. The blockade or reduction of choline-induced responses by bath application of nanomolar (nM) concentrations of MLA provided direct evidence that the choline responses were mediated by α7 nAChRs. Because choline is a partial agonist for α3β4 nAChRs (Alkondon et al., 1997), the residual choline responses are consistent with mediation by α3β4 nAChRs. Additionally, a subset of DS GCs responded to nicotine but not to choline, indicating the expression of a third nAChR subtype. The pharmacological results were supported by single cell reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry experiments. The expression of α7 and specific non-α7 nAChR subtypes was correlated with the preferred direction. This indicates the possibility of differential responses to ACh depending on the direction of movement. This is the first description of differential expression of multiple nAChR subtypes by DS GCs.

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Partial blockade of nicotinic acetylcholine receptors improves the counterregulatory response to hypoglycemia in recurrently hypoglycemic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00237.2014 ◽

2014 ◽

Vol 307 (7) ◽

pp. E580-E588 ◽

Cited By ~ 7

Author(s):

Edmund F. LaGamma ◽

Necla Kirtok ◽

Owen Chan ◽

Bistra B. Nankova

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Molecular Mechanisms ◽

Synaptic Activity ◽

Nicotinic Acetylcholine ◽

Mrna Induction

Recurrent exposure to hypoglycemia can impair the normal counterregulatory hormonal responses that guard against hypoglycemia, leading to hypoglycemia unawareness. This pathological condition known as hypoglycemia-associated autonomic failure (HAAF) is the main adverse consequence that prevents individuals with type 1 diabetes mellitus from attaining the long-term health benefits of tight glycemic control. The underlying molecular mechanisms responsible for the progressive loss of the epinephrine response to subsequent bouts of hypoglycemia, a hallmark sign of HAAF, are largely unknown. Normally, hypoglycemia triggers both the release and biosynthesis of epinephrine through activation of nicotinic acetylcholine receptors (nAChR) on the adrenal glands. We hypothesize that excessive cholinergic stimulation may contribute to impaired counterregulation. Here, we tested whether administration of the nAChR partial agonist cytisine to reduce postganglionic synaptic activity can preserve the counterregulatory hormone responses in an animal model of HAAF. Compared with nicotine, cytisine has limited efficacy to activate nAChRs and stimulate epinephrine release and synthesis. We evaluated adrenal catecholamine production and secretion in nondiabetic rats subjected to two daily episodes of hypoglycemia for 3 days, followed by a hyperinsulinemic hypoglycemic clamp on day 4. Recurrent hypoglycemia decreased epinephrine responses, and this was associated with suppressed TH mRNA induction (a measure of adrenal catecholamine synthetic capacity). Treatment with cytisine improved glucagon responses as well as epinephrine release and production in recurrently hypoglycemic animals. These data suggest that pharmacological manipulation of ganglionic nAChRs may be promising as a translational adjunctive therapy to avoid HAAF in type 1 diabetes mellitus.

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