scholarly journals M2 muscarinic receptor mediates arginine-vasopressin synthesis possibly through decreasing presynaptic GABA release in the supraoptic nuclei

2018 ◽  
Vol WCP2018 (0) ◽  
pp. PO1-1-126
Author(s):  
Hiroshi Nagano ◽  
Jeffrey G Tasker ◽  
Hayato Matsuyama ◽  
Yuki Sobue ◽  
Shoichiro Saito ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Arginine Vasopressin ◽  
Gaba Release ◽  
M2 Muscarinic Receptor ◽  
Vasopressin Synthesis ◽  
Supraoptic Nuclei

scholarly journals Muscarinic M2 receptor promotes vasopressin synthesis in mice supraoptic nuclei

2018 ◽  
Vol 237 (2) ◽  
pp. 207-216
Author(s):  
Hiroshi Nagano ◽  
Yuki Sobue ◽  
Hayato Matsuyama ◽  
Shoichiro Saito ◽  
Hiroki Sakai ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Knockout Mice ◽  
Receptor Expression ◽  
Muscarinic Agonist ◽  
Wild Type ◽  
Vasopressin Release ◽  
Paraventricular Nuclei ◽  
Vasopressin Secretion ◽  
Vasopressin Synthesis ◽  
Supraoptic Nuclei

Muscarinic acetylcholine receptors have been suggested to be implicated in arginine–vasopressin secretion because intracerebroventricular muscarinic agonist administration induces arginine–vasopressin release into the circulation. Although which subtype is involved in the regulation of arginine–vasopressin secretion is unclear, M2 receptors have been reported to be highly expressed in the hypothalamus. In the present study, M2 receptor-knockout mice were used to elucidate whether M2 receptor regulates arginine–vasopressin synthesis in the paraventricular nuclei and supraoptic nuclei of the hypothalamus. The number of arginine–vasopressin-immunoreactive neurons in M2 receptor-knockout mice was significantly decreased in the supraoptic nuclei, but not in the paraventricular nuclei compared with wild-type mice. Plasma arginine–vasopressin level in M2 receptor-knockout mice was also significantly lower than in the wild-type mice. Urinary volume and frequency as well as water intake in M2 receptor-knockout mice were significantly higher than those in wild-type mice. The V2 vasopressin receptor expression in kidneys of M2 receptor-knockout mice was comparable with that of wild-type mice, and increased urination in M2 receptor-knockout mice was significantly decreased by administration of desmopressin, a specific V2 receptor agonist, suggesting that V2 receptors in the kidneys of M2 receptor-knockout mice are intact. These results suggest that M2 receptors promote arginine–vasopressin synthesis in the supraoptic nuclei and play a role in the regulation and maintenance of body fluid.

Loss of M2 muscarinic receptor function inhibits development of hypoxic bradycardia and alters cardiac β-adrenergic sensitivity in larval zebrafish (Danio rerio)

2009 ◽  
Vol 297 (2) ◽  
pp. R412-R420 ◽  
Author(s):  
Shelby L. Steele ◽  
Kwok Hong Andy Lo ◽  
Vincent Wai Tsun Li ◽  
Shuk Han Cheng ◽  
Marc Ekker ◽  
...  
Keyword(s):  
Heart Rate ◽  
Muscarinic Receptor ◽  
Danio Rerio ◽  
Antisense Oligonucleotides ◽  
Adrenergic Receptor ◽  
Larval Zebrafish ◽  
M2 Muscarinic Receptor ◽  
Β Adrenergic Receptors ◽  
Relative Mrna Expression

Fish exposed to hypoxia develop decreased heart rate, or bradycardia, the physiological significance of which remains unknown. The general muscarinic receptor antagonist atropine abolishes the development of this hypoxic bradycardia, suggesting the involvement of muscarinic receptors. In this study, we tested the hypothesis that the hypoxic bradycardia is mediated specifically by stimulation of the M2 muscarinic receptor, the most abundant subtype in the vertebrate heart. Zebrafish ( Danio rerio) were reared at two levels of hypoxia (30 and 40 Torr Po2) from the point of fertilization. In hypoxic fish, the heart rate was significantly lower than in normoxic controls from 2 to 10 days postfertilization (dpf). At the more severe level of hypoxia (30 Torr Po2), there were significant increases in the relative mRNA expression of M 2 and the cardiac type β-adrenergic receptors ( β1AR, β2aAR, and β2bAR) at 4 dpf. The hypoxic bradycardia was abolished (at 40 Torr Po2) or significantly attenuated (at 30 Torr Po2) in larvae experiencing M2 receptor knockdown (using morpholino antisense oligonucleotides). Sham-injected larvae exhibited typical hypoxic bradycardia in both hypoxic regimens. The expression of β1AR, β2aAR, β2bAR, and M 2 mRNA was altered at various stages between 1 and 4 dpf in larvae experiencing M2 receptor knockdown. Interestingly, M2 receptor knockdown revealed a cardioinhibitory role for the β2-adrenergic receptor. This is the first study to demonstrate a specific role of the M2 muscarinic receptor in the initiation of hypoxic bradycardia in fish.

scholarly journals Impaired object-location learning and recognition memory but enhanced sustained attention in M2 muscarinic receptor-deficient mice

2018 ◽  
Vol 235 (12) ◽  
pp. 3495-3508
Author(s):  
Carola Romberg ◽  
Susan Bartko ◽  
Jürgen Wess ◽  
Lisa M. Saksida ◽  
Timothy J. Bussey
Keyword(s):  
Recognition Memory ◽  
Muscarinic Receptor ◽  
Sustained Attention ◽  
Object Location ◽  
M2 Muscarinic Receptor ◽  
Deficient Mice

Neuromuscular Relaxants as Antagonists for M2and M3Muscarinic Receptors 

1998 ◽  
Vol 88 (3) ◽  
pp. 744-750 ◽  
Author(s):  
Vivian Y. Hou ◽  
Carol A. Hirshman ◽  
Charles W. Emala
Keyword(s):  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Radioligand Binding ◽  
Chinese Hamster ◽  
Neuromuscular Relaxants ◽  
Ovary Cell ◽  
Relative Order ◽  
Parasympathetic Nerves ◽  
M2 Muscarinic Receptor ◽  
M3 Muscarinic Receptor

Background Neuromuscular relaxants such as pancuronium bind to M2 and M3 muscarinic receptors as antagonists. Blockade of muscarinic receptors in atria of the M2 subtype mediates tachycardia. In the lung, blockade of M2 receptors on parasympathetic nerves potentiates vagally induced bronchospasm, whereas blockade of M3 receptors on bronchial smooth muscle inhibits bronchospasm. The current study was designed to quantify the affinity of a series of neuromuscular relaxants for the M2 and M3 muscarinic receptors, which were individually stably transfected in Chinese hamster ovary cell lines. Methods Competitive radioligand binding assays determined the relative binding affinities of the neuromuscular relaxants pancuronium, succinylcholine, mivacurium, doxacurium, atracurium, rocuronium, gallamine, and pipecuronium for the muscarinic receptor in the presence of a muscarinic receptor antagonist (3H-QNB) in membranes prepared from cells individually expressing either the M2 or M3 muscarinic receptor. Results All muscle relaxants evaluated displaced 3H-QNB from muscarinic receptors. The relative order of potency for the M2 muscarinic receptor (highest to lowest) was pancuronium, gallamine, rocuronium, atracurium, pipecuronium, doxacurium, mivacurium, and succinylcholine. The relative order of potency for the M3 muscarinic receptor (highest to lowest) was pancuronium, atracurium, pipecuronium, rocuronium, mivacurium, gallamine, succinylcholine, and doxacurium. Conclusions All neuromuscular relaxants studied had affinities for the M2 and M3 muscarinic receptor, but only pancuronium and gallamine had affinities within the range of concentrations achieved with clinical use. The high affinities of gallamine and pancuronium for the M2 muscarinic receptor are consistent with a mechanism of M2 receptor blockade in relaxant-induced tachycardia.

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