Interaction of atrial muscarinic receptors with three kinds of GTP-binding proteins

Ikegaya, Takayoshi; Nishiyama, Terumasa; Haga, Kazuko; Haga, Tatsuya; Ichiyama, Arata; Kobayashi, Akira; Yamazaki, Noboru

doi:10.1016/0022-2828(90)91467-l

Cited by 27 publications

(26 citation statements)

References 20 publications

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“…The percentages and X, values of the high and low affinity sites were calculated from the displacement curves (Table DI). The results are consistent with the previous data obtained on reconstitution of G proteins with the M^ muscarinic receptor purified from porcine atria (37,38) or the M^ mutant from Sf9 cells (20), and can be explained with the same assumption; the Mj muscarinic receptor interacts with G o in the absence of GTP and the Mj-G,, complex exhibits higher affinity for carbamylcholine than the free M^ receptor, whereas M^-G,, and Mj exhibit the same affinity for atropine. The similarity in the proportions of high affinity sites in the absence of GTP indicate that the MBP-NLj mutant from E. coli has the same ability to couple with G protein G o as the Mj mutant from Sf9 (10).…”

Section: Expression Ofmuscarinic Receptor In E Colisupporting

confidence: 82%

Expression of Functional M2 Muscarinic Acetylcholine Receptor in Escherichia coli

Furukawa

Haga

2000

Journal of Biochemistry

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Section: Expression Ofmuscarinic Receptor In E Colisupporting

confidence: 82%

Expression of Functional M2 Muscarinic Acetylcholine Receptor in Escherichia coli

Furukawa

Haga

2000

Journal of Biochemistry

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“…Based on the present knowledge that all five subtypes are present in the brain, and that M 2 and M 4 receptors interact with Gi-type G proteins, it is reasonable to suppose that M 2 and M 4 receptors interact with Gi, Go and Gn. More specifically, Ikegaya et al 77) showed that muscarinic receptors purified from porcine atria (M 2 receptors) interact with three kinds of Gi-type G proteins, Gi, Go and Gn.…”

Section: Functions Of Muscarinic Receptorsmentioning

confidence: 99%

“…10 (a)). M 2 receptors are known to show high affinity for agonists when reconstituted with G proteins in the absence of guanine nucleotides, whereas they show low affinity for agonists in the absence of G proteins 74,77) (Fig. 3).…”

Section: Future Problemsmentioning

confidence: 99%

Molecular properties of muscarinic acetylcholine receptors

Haga

2013

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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101

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Muscarinic acetylcholine receptors, which comprise five subtypes (M1-M5 receptors), are expressed in both the CNS and PNS (particularly the target organs of parasympathetic neurons). M1-M5 receptors are integral membrane proteins with seven transmembrane segments, bind with acetylcholine (ACh) in the extracellular phase, and thereafter interact with and activate GTP-binding regulatory proteins (G proteins) in the intracellular phase: M1, M3, and M5 receptors interact with Gq-type G proteins, and M2 and M4 receptors with Gi/Go-type G proteins. Activated G proteins initiate a number of intracellular signal transduction systems. Agonist-bound muscarinic receptors are phosphorylated by G protein-coupled receptor kinases, which initiate their desensitization through uncoupling from G proteins, receptor internalization, and receptor breakdown (down regulation). Recently the crystal structures of M2 and M3 receptors were determined and are expected to contribute to the development of drugs targeted to muscarinic receptors. This paper summarizes the molecular properties of muscarinic receptors with reference to the historical background and bias to studies performed in our laboratories.

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“…Studies of signalling events on cloned muscarinic AChR subtypes have revealed differences in their abilities to modulate many different signal transduction pathways. The heart expresses only M2 receptors (Peterson et al, 1984) which are coupled to more than one G protein, regulating several signal transduction pathways (Brown et al, 1985a;Ashkenzi et al, 1989;Ikegaya et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Endogenous nitric oxide signalling system and the cardiac muscarinic acetylcholine receptor‐inotropic response

Sterin‐Borda

Echagüe

Leirós

et al. 1995

British J Pharmacology

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1 In this paper we have determined the different signalling pathways involved in muscarinic acetylcholine receptor (AChR)-dependent inhibition of contractility in rat isolated atria. 2 Carbachol stimulation of M2 muscarinic AChRs exerts a negative inotropic response, activation of phosphoinositide turnover, stimulation of nitric oxide synthase and increased production of cyclic GMP. 3 Inhibitors of phospholipase C, protein kinase C, calcium/calmodulin, nitric oxide synthase and guanylate cyclase, shifted the dose-response curve of carbachol on contractility to the right. These inhibitors also attenuated the muscarinic receptor-dependent increase in cyclic GMP and activation of nitric oxide synthase. In addition, sodium nitroprusside, isosorbide, or 8-bromo cyclic GMP, induced a negative inotropic effect, increased cyclic GMP and activated nitric oxide synthase. 4 These results suggest that carbachol activation of M2 AChRs, exerts a negative inotropic effect associated with increased production of nitric oxide and cyclic GMP. The mechanism appears to occur secondarily to stimulation of phosphoinositides turnover via phospholipase C activation. This in turn, triggers cascade reactions involving calcium/calmodulin and protein kinase C, leading to activation of nitric oxide synthase and soluble guanylate cyclase.

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Interaction of atrial muscarinic receptors with three kinds of GTP-binding proteins

Cited by 27 publications

References 20 publications

Expression of Functional M2 Muscarinic Acetylcholine Receptor in Escherichia coli

Expression of Functional M2 Muscarinic Acetylcholine Receptor in Escherichia coli

Molecular properties of muscarinic acetylcholine receptors

Endogenous nitric oxide signalling system and the cardiac muscarinic acetylcholine receptor‐inotropic response

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