Distribution of muscarinic receptors on the endothelium of cortical vessels in the rat brain

Badaut, Jérôme; Moro, Véronique; Seylaz, Jacques; Lasbennes, François

doi:10.1016/s0006-8993(97)00999-2

Cited by 12 publications

(7 citation statements)

References 37 publications

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“…Rather, we support vasodilatation-associated muscarinic reactions in brain vessels [33]. Extending previous reports of inhibition of serum AChE by SSRI's [12], our results attribute the fluoxetine-mediated AChE inhibition within brain vessels, to the presence of albumin which would increase the levels of ACh in the micro-environment of endothelial cells.…”

Section: Discussionsupporting

confidence: 89%

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

Ofek

Schoknecht

Melamed-Book

et al. 2012

J Cellular Molecular Medi

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Ischaemic stroke patients treated with Selective Serotonin Reuptake Inhibitors (SSRI) show improved motor, cognitive and executive functions, but the underlying mechanism(s) are incompletely understood. Here, we report that cerebral arterioles in the rat brain superfused with therapeutically effective doses of the SSRI fluoxetine showed consistent, dose-dependent vasodilatation (by 1.2 to 1.6-fold), suppressible by muscarinic and nitric oxide synthase (NOS) antagonists [atropine, NG-nitro-l-arginine methyl ester (l-NAME)] but resistant to nicotinic and serotoninergic antagonists (mecamylamine, methylsergide). Fluoxetine administered 10–30 min. following experimental vascular photo-thrombosis increased arterial diameter (1.3–1.6), inducing partial, but lasting reperfusion of the ischaemic brain. In brain endothelial b.End.3 cells, fluoxetine induced rapid muscarinic receptor-dependent increases in intracellular [Ca2+] and promoted albumin- and eNOS-dependent nitric oxide (NO) production and HSP90 interaction. In vitro, fluoxetine suppressed recombinant human acetylcholinesterase (rhAChE) activity only in the presence of albumin. That fluoxetine induces vasodilatation of cerebral arterioles suggests co-promotion of endothelial muscarinic and nitric oxide signalling, facilitated by albumin-dependent inhibition of serum AChE.

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Section: Discussionsupporting

confidence: 89%

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

Ofek

Schoknecht

Melamed-Book

et al. 2012

J Cellular Molecular Medi

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“…Bars 25 μm presumably being mediated by the endothelial production of nitric oxide (Pesic et al 2003). In accordance with several previous reports describing the location of muscarinic ACh receptors in blood vessel walls in other tissues (e.g., Badaut et al 1997), we have found M 2 R immunoreactivity to be mainly localized to the endothelial part of the vessels. This observation suggests the occurrence of ACh-mediated vasodilatory mechanisms in the Achilles tendon.…”

Section: Presence Of M 2 Immunoreactivity In Cells In Blood Vessel Wasupporting

confidence: 92%

Presence of a non-neuronal cholinergic system and occurrence of up- and down-regulation in expression of M2 muscarinic acetylcholine receptors: new aspects of importance regarding Achilles tendon tendinosis (tendinopathy)

et al. 2007

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Limited information is available concerning the existence of a cholinergic system in the human Achilles tendon. We have studied pain-free normal Achilles tendons and chronically painful Achilles tendinosis tendons with regard to immunohistochemical expression patterns of the M(2) muscarinic acetylcholine receptor (M(2)R), choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT). M(2)R immunoreactivity was detected in the walls of blood vessels. As evidenced via parallel staining for CD31 and alpha-smooth muscle actin, most M(2)R immunoreactivity was present in the endothelium. M(2)R immunoreactivity also occured in tenocytes, which regularly immunoreact for vimentin. The degree of M(2)R immunoreactivity was highly variable, tendinosis tendons that exhibit hypercellularity and hypervascularity showing the highest levels of immunostaining. Immunoreaction for ChAT and VAChT was detected in tenocytes in tendinosis specimens, particularly in aberrant cells. In situ hybridization revealed that mRNA for ChAT is present in tenocytes in tendinosis specimens. Our results suggest that autocrine/paracrine effects occur concerning the tenocytes in tendinosis. Up-regulation/down-regulation in the levels of M(2)R immunoreactivity possibly take place in tenocytes and blood vessel cells during the various stages of tendinosis. The presumed local production of acetylcholine (ACh), as evidenced by immunoreactivity for ChAT and VAChT and the detection of ChAT mRNA, appears to evolve in response to tendinosis. These observations are of importance because of the well-known vasoactive, trophic, and pain-modulating effects that ACh is known to have and do unexpectedly establish the presence of a non-neuronal cholinergic system in the Achilles tendon.

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“…A number of studies have indicated that endothelial cells are able to synthesize and release ACh (Kummer and Haberberger, 1999). Muscarinic ACh receptors (mAChR) have been demonstrated on the endothelium of cerebral vessels (Badaut et al, 1997;Phillips et al, 1997) and activation of endothelial mAChRs trigger a release of nitric oxide (NO), which is suggested to be the actual vasorelaxing agent (Faraci and Sigmund, 1999;Furchgott and Zawadzki, 1980;Huang et al, 1995;Meng et al, 1996;Rosenblum, 1986;Sobey and Faraci, 1997). Moreover, nicotinic ACh receptors (nAChR) are also expressed on brain endothelial cells (Bruggmann et al, 2002) and nicotine and its major metabolite, cotinine, increase cerebral microvascular permeability via nAChR (Abbruscato et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Abnormal cholinergic and GABAergic vascular innervation in the hypothalamic arcuate nucleus of obese tub/tub mice

Bäckberg

Meister

2004

Synapse

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Tubby and tubby-like proteins (TULPs) are encoded by members of a small gene family. An autosomal recessive mutation in the mouse tub gene leads to blindness, deafness, and maturity-onset obesity. The mechanisms by which the mutation causes the obesity syndrome has not been established. We compared obese tub/tub mice and their lean littermates in order to find abnormalities within the mediobasal hypothalamus, a region intimately associated with the regulation of body weight. Using an antiserum to the vesicular acetylcholine transporter (VAChT), a marker for cholinergic neurons, many unusually large VAChT-immunoreactive (-ir) nerve terminals, identified by colocalization with the synaptic vesicle protein synaptophysin, were demonstrated in the hypothalamic arcuate nucleus of obese tub/tub mice. Double-labeling showed that VAChT-ir nerve endings also contained glutamic acid decarboxylase (GAD), a marker for ␥-aminobutyric acid (GABA) neurons. The VAChT-and GAD-ir nerve terminals were in close contact with blood vessels, identified with antisera to platelet endothelial cell adhesion molecule-1 (PECAM; also called CD31), laminin, smooth muscle actin (SMA), and glucose transporter-1 (GLUT1). Such large cholinergic and GABAergic nerve terminals surrounding blood vessels were not seen in the arcuate nucleus of lean tub/ϩ mice. The presence of abnormal cholinergic/GABAergic vascular innervation in the arcuate nucleus suggests that alterations in this region, which contains neurons that receive information from the periphery and which relays information about the energy status to other parts of the brain, may be central in the development of the obese phenotype in animals with an autosomal recessive mutation in the tub gene. Synapse 52:245-257, 2004.

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Distribution of muscarinic receptors on the endothelium of cortical vessels in the rat brain

Cited by 12 publications

References 37 publications

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

Fluoxetine induces vasodilatation of cerebral arterioles by co‐modulating NO/muscarinic signalling

Presence of a non-neuronal cholinergic system and occurrence of up- and down-regulation in expression of M2 muscarinic acetylcholine receptors: new aspects of importance regarding Achilles tendon tendinosis (tendinopathy)

Abnormal cholinergic and GABAergic vascular innervation in the hypothalamic arcuate nucleus of obese tub/tub mice

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