Cyclic GMP formation induced by muscarinic receptors is mediated by nitric oxide synthesis in rat cortical primary cultures

Castoldi, Anna Federica; Manzo, Luigi; Costa, Lucio G.

doi:10.1016/0006-8993(93)91216-f

Cited by 39 publications

(23 citation statements)

References 24 publications

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“…This response has been shown both in vivo [Lenox et al, 1980] and in vitro [Castoldi et al, 1993]. Activation of guanylyl cyclase via muscarinic receptors is attenuated by inhibitors of NO synthase and by hemoglobin, demonstrating that it is the result of NO generation [Castoldi et al, 1993]. In addition, similar results have been obtained in neuronal cell lines [Hu and El-Fakahany, 1993].…”

Section: Muscarinic Receptor-mediated Activation Of No Synthase In Nesupporting

confidence: 77%

“…A half-maximal stimulatory response is induced at 26 µM carbachol. The cyclic GMP response is attenuated by inhibitors of NO synthase and by hemoglobin, demonstrating that it is the result of NO generation [Castoldi et al, 1993].…”

Section: Pharmacology Of Muscarinic Receptors Coupled To Generation Omentioning

confidence: 99%

“…NO synthase-mediated conversion of L-arginine to L-citrulline. et al, 1990;Hu and El-Fakahany, 1993], rat cortical primary cultures [Castoldi et al, 1993], bovine lung artery [Ignarro et al, 1986], rat ventricular myocytes [Balligand et al, 1993], pancreatic acinar cells [Gukovskaya and Pandol, 1994], and vascular smooth muscle [Furchgott and Zawadzki, 1980;Palmer et al, 1987;Ignarro et al, 1988;Furchgott and Vanhoutte, 1989]. …”

Section: Activation Of Guanylyl Cyclase By Nomentioning

confidence: 99%

“…Activation of muscarinic receptors in rat primary cortical neuron cultures increases the level of cyclic GMP [Castoldi et al, 1993]. Maximal stimulation takes place at 2 min, followed by a slow decline.…”

Section: Pharmacology Of Muscarinic Receptors Coupled To Generation Omentioning

confidence: 99%

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Muscarinic receptor-mediated activation of nitric oxide synthase

Wotta

El‐Fakahany

1997

Drug Dev. Res.

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The potent vasodilator factor released from endothelial cells upon activation of muscarinic acetylcholine receptors has recently been identified as nitric oxide (NO). This discovery has sparked intensive research efforts aiming at understanding the functional role of this short‐lived, highly reactive free radical. As a result, it has been shown that NO is a very important second messenger involved in a wide spectrum of physiological functions. One important aspect that differentiates NO from other second messengers is that NO is a ‘traveling’ messenger that diffuses out of the cells of its origin to produce marked effects in neighboring cells. This paper provides a synopsis of the diverse biological roles of NO and the mechanisms of its generation upon activation of muscarinic acetylcholine receptors. Drug Dev. Res. 40:205–214, 1997. © 1997 Wiley‐Liss, Inc.

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Section: Muscarinic Receptor-mediated Activation Of No Synthase In Nesupporting

confidence: 77%

Section: Pharmacology Of Muscarinic Receptors Coupled To Generation Omentioning

confidence: 99%

Section: Activation Of Guanylyl Cyclase By Nomentioning

confidence: 99%

Section: Pharmacology Of Muscarinic Receptors Coupled To Generation Omentioning

confidence: 99%

See 2 more Smart Citations

Muscarinic receptor-mediated activation of nitric oxide synthase

Wotta

El‐Fakahany

1997

Drug Dev. Res.

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“…These channels may be activated by both dendritic and backpropagating action potentials that can lead to an increased calcium concentration, providing temporal specificity to this synapse-specific modulation. Muscarinic (especially M 1 ) receptor activation, elevating local calcium concentrations, may also trigger the nNOS-NO-NOsGC-cGMP pathway, as it was shown in several paradigms (Castoldi et al, 1993;Hu and elFakahany, 1993;Ando et al, 1994;Mathes and Thompson, 1996;Liu et al, 1997;Borda et al, 2005;Cuadra and ElFakahany, 2005). In addition, muscarinic enhancement of R-type calcium currents has also been observed in hippocampal pyramidal neurons (Tai et al, 2006), whereas M 1 receptors are widely expressed in pyramidal cells (Levey et al, 1995(Levey et al, , 1996.…”

Section: Synapse-specific No Production In Gabaergic Synapsesmentioning

confidence: 94%

Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling

Szabadits¹,

Cserép²,

Ludányi³

et al. 2007

J. Neurosci.

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Nitric oxide (NO) plays an important role in synaptic plasticity as a retrograde messenger at glutamatergic synapses. Here we describe that, in hippocampal pyramidal cells, neuronal nitric oxide synthase (nNOS) is also associated with the postsynaptic active zones of GABAergic symmetrical synapses terminating on their somata, dendrites, and axon initial segments in both mice and rats. The NO receptor nitric oxide-sensitive guanylyl cyclase (NOsGC) is present in the brain in two functional subunit compositions: ␣ 1 ␤ 1 and ␣ 2 ␤ 1 . The ␤ 1 subunit is expressed in both pyramidal cells and interneurons in the hippocampus. Using immunohistochemistry and in situ hybridization methods, we describe that the ␣ 1 subunit is detectable only in interneurons, which are always positive for ␤ 1 subunit as well; however, pyramidal cells are labeled only for ␤ 1 and ␣ 2 subunits. With double-immunofluorescent staining, we also found that most cholecystokinin-and parvalbumin-positive and smaller proportion of the somatostatin-and nNOS-positive interneurons are ␣ 1 subunit positive. We also found that the ␣ 1 subunit is present in parvalbumin-and cholecystokinin-positive interneuron terminals that establish synapses on somata, dendrites, or axon initial segments. Our results demonstrate that NOsGC, composed of ␣ 1 ␤ 1 subunits, is selectively expressed in different types of interneurons and is present in their presynaptic GABAergic terminals, in which it may serve as a receptor for NO produced postsynaptically by nNOS in the very same synapse.

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Localization of the m2 muscarinic acetylcholine receptor protein and mRNA in cortical neurons of the normal and cholinergically deafferented rhesus monkey

et al. 1998

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The m2 muscarinic acetylcholine receptor in the cerebral cortex has traditionally been thought of as an autoreceptor located on cholinergic fibers that originate from neurons in the nucleus basalis of Meynert. We now provide evidence for widespread localization of the m2 receptor in noncholinergic neurons and fibers of the cerebral cortex. The cellular and subcellular distribution of the m2 receptor protein and mRNA were examined in normal monkeys and in monkeys in which the cortical cholinergic afferents were selectively lesioned by injection of the specific immunotoxin, anti-p75NTR-saporin into the nucleus basalis. Both in normal and immunolesioned monkeys, the m2 mRNA and protein were localized in pyramidal and nonpyramidal neurons. In pyramidal neurons, membrane-associated receptor immunoreactivity was found exclusively in dendritic spines receiving asymmetric synapses, indicating that the m2 receptor may modulate excitatory neurotransmission at these sites. In nonpyramidal neurons, the m2 immunoreactivity was present along the cytoplasmic surface of membranes in cell bodies, dendrites and axons. Both in pyramidal and nonpyramidal neurons of normal and lesioned monkeys, the m2 receptor was located peri- and extra-synaptically, suggesting that it may be contacted by acetylcholine via volume transmission. The localization of the m2 receptor in cortical neurons and the sparing of m2 immunoreactivity in lesioned monkeys indicates that the m2 receptor is synthesized largely within the cortex and/or is localized to noncholinergic terminals of either intrinsic or extrinsic origin. These findings open the possibility that the loss of the m2 receptor in Alzheimer's disease may in part be due to degenerative changes in m2 positive neurons of the cortex rather than entirely due to the loss of autoreceptors.

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Cyclic GMP formation induced by muscarinic receptors is mediated by nitric oxide synthesis in rat cortical primary cultures

Cited by 39 publications

References 24 publications

Muscarinic receptor-mediated activation of nitric oxide synthase

Muscarinic receptor-mediated activation of nitric oxide synthase

Hippocampal GABAergic Synapses Possess the Molecular Machinery for Retrograde Nitric Oxide Signaling

Localization of the m2 muscarinic acetylcholine receptor protein and mRNA in cortical neurons of the normal and cholinergically deafferented rhesus monkey

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