Distribution of muscarinic receptor subtypes in rat brain from postnatal to old age

Tice, Melissa A.B.; Hashemi, Tanaz; Taylor, Lisa A.; McQuade, Robert D.

doi:10.1016/0165-3806(95)01515-9

Cited by 82 publications

(51 citation statements)

References 26 publications

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“…␤-Actin (Sigma-Aldrich) was used as a housekeeping protein to control the quantity of proteins included in the Western blot analyses. To check whether the anti-M 1 , M 2 , and M 3 Abs were specific for the single MR subtype and did not cross-react with other subtypes or with nicotinic receptors (Tice et al, 1996) and to check the molecular weight of ChAT and MRs, soluble recombinant peptides M 1 (Santa Cruz Biotechnology, Inc.; 50 g), M 2 (Sigma-Aldrich; 30 g), and M 3 (Sigma-Aldrich; 50 g) were used.…”

Section: Methodsmentioning

confidence: 99%

Smoke, Choline Acetyltransferase, Muscarinic Receptors, and Fibroblast Proliferation in Chronic Obstructive Pulmonary Disease

Profita¹,

Bonanno²,

Siena³

et al. 2009

J Pharmacol Exp Ther

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Acetylcholine (ACh), synthesized by choline acetyltransferase (ChAT), and muscarinic M 1 , M 2 , and M 3 receptors (MRs) are involved in fibroblast proliferation. We evaluated ChAT, MRs, and extracellular signal-regulated kinase (ERK) 1/2 and nuclear factor (NF) B activation in lung fibroblasts from patients with chronic obstructive pulmonary disease (COPD), control smokers, and controls. Human fetal lung fibroblasts (HFL-1) stimulated with interleukin (IL)-1␤, tumor necrosis factor (TNF)-␣, and cigarette smoke extracts (CSEs) were evaluated for ChAT and MR expression. We tested the effects of ACh on fibroblast proliferation and its ability to bind fibroblasts from patients with COPD, control smokers, controls, and HFL-1 stimulated with IL-1␤, TNF-␣, and CSE. ChAT, M 1 , and M 3 expression and ERK1/2 and NFB activation were increased, whereas M 2 was reduced, in COPD and smoker subjects compared with controls. IL-1␤ increased the ChAT and M 3 , TNF-␣ down-regulated M 2 , and CSE increased ChAT and M 3 expression while downregulating the expression of M 2 in HFL-1 cells. ACh stimulation increased fibroblast proliferation in patients with COPD, control smokers, and controls, with higher effect in control smokers and patients with COPD and increased HFL-1 proliferation only in CSE-treated cells. The binding of ACh was higher in patients with COPD and in control smokers than in controls and in CSE-treated than in IL-1␤-and TNF-␣-stimulated HFL-1 cells. Tiotropium (Spiriva; [1␣,2␤,4␤,5␣,7␤-7-hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatrcyclo[3.3. [(E)-3-(4-methylphenylsulfonyl)-2-propenetrile, C 10 H 9 NO 2 C], down-regulated the ACh-induced fibroblast proliferation, promoting the MRs and ERK1/2 and NFB pathways involvement in this phenomenon. These results suggest that cigarette smoke might alter the expression of ChAT and MRs, promoting airway remodeling in COPD and that anticholinergic drugs, including tiotropium, might prevent these events.An overpresence of fibroblasts has been observed in chronic airway diseases and several factors, released by both parenchymal and inflammatory cells, can contribute to this event promoting fibroblast proliferation (Jeffery, 1998 ABBREVIATIONS: M 1 , muscarinic M 1 receptor; M 2 , muscarinic M 2 receptor; M 3 , muscarinic M 3 receptor; MR, muscarinic M 1 , M 2 , and M 3 receptor; MAPK, mitogen-activated protein kinase; ACh, acetylcholine; ChAT, choline acetyltransferase; COPD, chronic obstructive pulmonary disease; IL, interleukin; TNF, tumor necrosis factor; CS, cigarette smoke; ERK, extracellular signal-regulated kinase; NF, nuclear factor; CSE, cigarette smoke extract; C, asymptomatic nonsmoking subject(s) with normal lung function; FBS, fetal bovine serum; PAGE, polyacrylamide gel electrophoresis; FITC, fluorescein isothiocyanate; ELISA, enzyme-linked immunosorbent assay; pNFB, phosphorylated NFB; tNFB, total NFB; tiotropium, Spiriva, [1␣,2␤,4␤,5␣,7␤-7-hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatrcyclo[3.3. O; 4-DAMP, 4-diphenylacetoxy-N...

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Section: Methodsmentioning

confidence: 99%

Smoke, Choline Acetyltransferase, Muscarinic Receptors, and Fibroblast Proliferation in Chronic Obstructive Pulmonary Disease

Profita¹,

Bonanno²,

Siena³

et al. 2009

J Pharmacol Exp Ther

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“…One neuromodulator that may function in this role is acetylcholine, which has been shown to affect synaptic plasticity in the hippocampus, visual cortex, and dorsal cochlear nucleus (DCN; a cerebellum-like structure) through the activation of muscarinic acetylcholine receptors (mAChRs) (4)(5)(6)(7)(8). There are five known isoforms of mAChRs (designated M1-5), each of which exhibits a heterogeneous distribution pattern across different brain areas (9)(10)(11). All five isoforms are expressed in the cerebellar cortex (12) and are found predominantly in lobules IX and X (13), which form the bulk of the vestibulocerebellum.…”

mentioning

confidence: 99%

Muscarinic acetylcholine receptor activation blocks long-term potentiation at cerebellar parallel fiber–Purkinje cell synapses via cannabinoid signaling

Rinaldo

Hansel

2013

Proc. Natl. Acad. Sci. U.S.A.

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Muscarinic acetylcholine receptors (mAChRs) are known to modulate synaptic plasticity in various brain areas. A signaling pathway triggered by mAChR activation is the production and release of endocannabinoids that bind to type 1 cannabinoid receptors (CB1R) located on synaptic terminals. Using whole-cell patch-clamp recordings from rat cerebellar slices, we have demonstrated that the muscarinic agonist oxotremorine-m (oxo-m) blocks the induction of presynaptic long-term potentiation (LTP) at parallel fiber (PF)-Purkinje cell synapses in a CB1R-dependent manner. Under control conditions, LTP was induced by delivering 120 PF stimuli at 8 Hz. In contrast, no LTP was observed when oxo-m was present during tetanization. PF-LTP was restored when the CB1R antagonist N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (AM251) was coapplied with oxo-m. Furthermore, the suppressive effect of oxo-m on PF-LTP was abrogated by the GDP analog GDP-β-S (applied intracellularly), the phospholipase C inhibitor U-73122, and the diacylglycerol lipase inhibitor tetrahydrolipstatin (THL), suggesting that cannabinoid synthesis results from the activation of G q -coupled mAChRs present on Purkinje cells. The oxo-m-mediated suppression of LTP was also prevented in the presence of the M3 receptor antagonist DAU 5884, and was absent in M1/M3 receptor double-KO mice, identifying M3 receptors as primary oxo-m targets. Our findings allow for the possibility that cholinergic signaling in the cerebellum-which may result from long-term depression (LTD)-related disinhibition of cholinergic neurons in the vestibular nuclei-suppresses presynaptic LTP to prevent an up-regulation of transmitter release that opposes the reduction of postsynaptic responsiveness. This modulatory capacity of mAChR signaling could promote the functional penetrance of LTD.vestibulocerebellum | learning | retrograde signaling L ong-lasting changes in synaptic efficacy at parallel fiber (PF)-Purkinje cell synapses are widely considered to be a requisite for cerebellar motor learning (1-3). Neuromodulators that can shift the induction probabilities for various types of plasticity at this synapse may thus fine-tune the conditions under which motor learning can occur. One neuromodulator that may function in this role is acetylcholine, which has been shown to affect synaptic plasticity in the hippocampus, visual cortex, and dorsal cochlear nucleus (DCN; a cerebellum-like structure) through the activation of muscarinic acetylcholine receptors (mAChRs) (4-8). There are five known isoforms of mAChRs (designated M1-5), each of which exhibits a heterogeneous distribution pattern across different brain areas (9-11). All five isoforms are expressed in the cerebellar cortex (12) and are found predominantly in lobules IX and X (13), which form the bulk of the vestibulocerebellum. Cholinergic cerebellar afferents to this area are believed to originate from the vestibular nuclei of the brainstem (14, 15), and within these lobules the action of ace...

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“…During this period of development, choline acetyltransferase levels are relatively higher than levels of the degradative enzyme for acetylcholine, acetylcholinesterase (Boegman et al, 1988;Clos et al, 1989;Court et al, 1993). A developmental role for cholinergic agonists is further strengthened by several reports indicating that both muscarinic and nicotinic (nAChR) cholinergic receptor subtypes are present in perinatal periods in rats (Zoli et al, 1995;Tice et al, 1996;Winzer-Serhan & Leslie, 1997) and humans (Kinney et al, 1993;Court et al, 1995). In particular, previous studies have demonstrated nAChRs in granule and Purkinje neurons in rats (Zoli et al, 1995;Dominguez et al, 1997;Morley, 1997) and in the external granular layer (EGL), the location of granule neuron precursors, in humans (Court et al, 1995).…”

Section: Introductionmentioning

confidence: 77%

Effect of nicotine on cerebellar granule neuron development

Opanashuk¹,

Pauly²,

Hauser³

2001

Eur J Neurosci

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To assess the role of nicotinic cholinergic receptors (nAChR) on neuronal maturation, nAChR expression and the direct effects of nAChR activation were examined in cerebellar external granular layer (EGL) precursors isolated in vitro. Treatment of EGL neuroblasts with nicotine elicited a concentration-dependent increase in DNA content and synthesis, implying an increase in cell numbers. Pretreatment of cultures with the nAChR antagonist dihydro-β-erythroidine (DHBE) attenuated nicotine-induced changes in DNA abundance and synthesis. Furthermore, chronic nicotine treatment for 4-7 days promoted EGL cell survival. Epibatidine but not cytisine stimulated granule neuroblast DNA synthesis and survival. Survival effects mediated by nicotine and epibatidine were attenuated by pre-treating cultures with DHBE. Immunocytochemical analysis revealed that EGL neurons possessed α3, but not α4, nAChR immunoreactivity. Quantitative autoradiography was used to determine which nAChRs are present during the period of granule cell neurogenesis in vivo. On postnatal day 5, the EGL was intensely labeled by [ 3 H]-epibatidine but virtually devoid of [ 3 H]-A85380 binding suggesting that a high concentration of α3 nAChRs is present in granule neuroblasts. The pharmacology of [ 3 H]-epibatidine displacement from EGL neurons also suggested an interaction with the α3-nAChR subunits. Together these data provide novel evidence that the activation of nAChRs directly affect the development of primary cerebellar neuroblasts and further suggest that the effects are mediated through the α3-nAChR subtype.

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Distribution of muscarinic receptor subtypes in rat brain from postnatal to old age

Cited by 82 publications

References 26 publications

Smoke, Choline Acetyltransferase, Muscarinic Receptors, and Fibroblast Proliferation in Chronic Obstructive Pulmonary Disease

Smoke, Choline Acetyltransferase, Muscarinic Receptors, and Fibroblast Proliferation in Chronic Obstructive Pulmonary Disease

Muscarinic acetylcholine receptor activation blocks long-term potentiation at cerebellar parallel fiber–Purkinje cell synapses via cannabinoid signaling

Effect of nicotine on cerebellar granule neuron development

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