Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor

Kubo, Tai; Fukuda, Kazuhiko; Mikami, Atsushi; Maeda, Akito; Takahashi, Hideo; Mishina, Masayoshi; Haga, Tatsuya; Haga, Kazuko; Ichiyama, Arata; Kangawa, Kenji; Kojima, Masayasu; Matsuo, Hisayuki; Hirose, Tatsuro; Numa, Shosaku

doi:10.1038/323411a0

Cited by 882 publications

(262 citation statements)

References 56 publications

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“…22,23 Acetylcholine is stored in vesicles and is released by parasympathetic stimulation, activating primarily postsynaptic muscarinic and preganglionic nicotinic receptors. 24,25 The effects are terminated by rapid degradation by acetylcholinerases. 26 Increased parasympathetic stimulation decreases heart rate by decreasing SA node discharge rate and AV node conduction velocity.…”

Section: Effects Of the Sympathetic Nervous System On The Normal Myocmentioning

confidence: 99%

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Vaseghi

Shivkumar²

2008

Progress in Cardiovascular Diseases

320

227

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The cardiac autonomic nervous system consists of 2 branches-the sympathetic and the parasympathetic systems-that work in a delicately tuned, yet opposing fashion in the heart. This extrinsic control mechanism can dominate intrinsic regulatory mechanisms that modulate heart rate and cardiac output. These branches differ in their neurotransmitters (norepinephrine and acetylcholine) and exert stimulatory or inhibitory effects on target tissue via adrenergic and muscarinic receptors. Stimulation of the sympathetic branch exerts facilitatory effects on function, increasing heart rate and myocardial contractility, whereas the stimulation of the parasympathetic branch exerts inhibitory effects that decrease heart rate and contractility. The interplay between these two branches is complex and susceptible to control at several levels, from centrally mediated baroreceptors and chemoreceptors to local interneuronal interactions.Alterations in autonomic function occur in several interrelated cardiac conditions including sudden cardiac death, congestive heart failure, diabetic neuropathy, and myocardial ischemia. Although the full extent of these changes has not been elucidated, multiple autonomic remodeling mechanisms have been observed at both the neuronal fiber and myocardial cellular level that contribute to an arrhythmogenic substrate. We describe the anatomy of both systems in this review. However, the review will premdominantly focus on the sympathetic system, whose role in the modulation of cardiac arrhythmias is slightly better delineated. Cardiac Autonomic Innervation: NeuroanatomyBoth branches of the autonomic nervous system are composed of both afferent and efferent as well interneuronal fibers (Fig 1). Sympathetic innervation originates mainly in the right and left stellate ganglia. These fibers travel along the epicardial vascular structures of the heart and penetrate into the underlying myocardium similar to coronary vessels and end as sympathetic nerve terminals reaching the endocardium. Based on norepinephrine content studies, a gradient exists in sympathetic innervation from atria to the ventricles and from base to apex of the heart. Therefore, the atria are most densely innervated, but the ventricles are also supplied with a sympathetic network, most densely at the base. 1 Parasympathetic effects are carried by the right and left vagus nerves, originating in the medulla. The vagus nerve further divides into the superior and inferior cardiac nerves, finally merging with the postganglionic sympathetic neurons to form a plexus of nerves at the base of the heart, known as the cardiac plexus. In contrast to sympathetic neurons, after parasympathetic fibers cross the atrioventricular (AV) groove along the surface of the heart,

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Section: Effects Of the Sympathetic Nervous System On The Normal Myocmentioning

confidence: 99%

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Vaseghi

Shivkumar²

2008

Progress in Cardiovascular Diseases

320

227

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“…Muscarinic cholinergic receptors belong to the superfamily of G-protein coupled receptors [42][43][44] that either activate or inhibit message transduction systems, thus having an effect on the intracellular second messengers such as cyclic AMP (cAMP) or inositol triphosphate (IP 3 ). Muscarinic receptors consist of seven transmembrane-spanning domains and are composed of 460-590 amino acids.…”

Section: Muscarinic Receptorsmentioning

confidence: 99%

Towards a muscarinic hypothesis of schizophrenia

Raedler

Bymaster

Tandon³

et al. 2006

Mol Psychiatry

243

209

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Although the neurotransmitter dopamine plays a prominent role in the pathogenesis and treatment of schizophrenia, the dopamine hypothesis of schizophrenia fails to explain all aspects of this disorder. It is increasingly evident that the pathology of schizophrenia also involves other neurotransmitter systems. Data from many streams of research including preclinical and clinical pharmacology, treatment studies, post-mortem studies and neuroimaging suggest an important role for the muscarinic cholinergic system in the pathophysiology of schizophrenia. This review will focus on evidence that supports the hypothesis that the muscarinic system is involved in the pathogenesis of schizophrenia and that muscarinic receptors may represent promising novel targets for the treatment of this disorder.

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“…Expression in Xenopus oocytes of cloned DNAs encoding four individual mAChR subtypes has revealed that mAChR I and mAChR III mediate activation of a Ca2+-dependent C1-current, whereas mAChR II and mAChR IV principally induce activation of Na ÷ and K ÷ currents in a Ca2+-independent manner [2][3][4]. Expression studies in mammalian cells have further shown that mAChR I and mAChR III are coupled efficiently with phosphoinositide hydrolysis [5][6][7], intracellular Ca 2÷ release [8], ac- Abbreviations: mAChR, muscarinic acetylcholine receptor; ACh, acetylcholine; NMS, N-methylscopolamine; QNB, quinuclidinyl benzilate tivation of Ca2+-dependent K ÷ currents [5,8,9] and inhibition of the M-current [5,8], whereas mAChR II and mAChR IV are linked preferentially with adenylate cyclase inhibition [6,10].…”

Section: Introductionmentioning

confidence: 99%

“…The antagonist binding properties of individual mAChR subtypes expressed in Xenopus oocytes [2,3,12] show that mAChR I, mAChR II and mAChR III correspond most closely to the pharmacologically defined M1 (I), M2 cardiac (II) and M2 glandular (III) subtypes [13][14][15], respectively. This, together with the differential tissue distribution of the mRNAs encoding the individual mAChR species [2,[16][17][18][19], indicates that the mAChR heterogeneity in tissues with respect to antagonist binding is attributable to the presence of distinct mAChR gene products by themselves or in various combinations.…”

Section: Introductionmentioning

confidence: 99%

Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling

et al. 1988

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Chimaeric muscarinic acetylcholine receptors (mAChR) in which corresponding portions of mAChR I and mAChR II are replaced with each other have been produced in Jfenopus oocytes by expression of cDNA constructs encoding them.Functional analysis of the chimaeric mAChRs indicates that a region mostly comprising the putative cytoplasmic portion between the proposed transmembrane segments V and VI is involved in selective coupling of mAChR I and mAChR II with different effector systems. In contrast, the exchange of this region between mAChR I and mAChR II does not significantly affect the antagonist binding properties of the two mAChR subtypes.

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Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor

Cited by 882 publications

References 56 publications

The Role of the Autonomic Nervous System in Sudden Cardiac Death

The Role of the Autonomic Nervous System in Sudden Cardiac Death

Towards a muscarinic hypothesis of schizophrenia

Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling

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