INCREASE OF ACETYLCHOLINE‐RECEPTOR SENSITIVITY BY ADENOSINE TRIPHOSPHATE: A NOVEL ACTION OF ATP ON ACh‐SENSITIVITY

Akasu, Takashi; Hirai, Keiji; Koketsu, K.

doi:10.1111/j.1476-5381.1981.tb09997.x

Cited by 105 publications

(43 citation statements)

References 4 publications

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“…This was confirmed by AKASU et al [4], who analyzed the facilitatory action of ATP on the sensitivity of nicotinic ACh-receptors. The amplitude of the ACh-current recorded at the frog skeletal muscle end-plate was increased by ATP.…”

Section: A) Experimental Evidencesupporting

confidence: 63%

“…This potentiation was not due to an effect of ATP on cholinesterases, since the increase of sensitivity could also be demonstrated with carbachol. Kinetic analysis of the effect of ATP on the dose-response relationship of the carbachol-current indicated that ATP increased the ACh-sensitivity without changing the affinity of ACh for its recognition site [4,5].…”

Section: A) Experimental Evidencementioning

confidence: 99%

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Modulation of receptor sensitivity and action potentials by transmitters in vertebrate neurones.

Koketsu

1984

Jpn.J.Physiol

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According to the classical concept of synaptic transmission, it occurs at a synapse where a presynaptic nerve terminal (synaptic knob) comes in close contact with the subsynaptic membrane of a postsynaptic neurone. A very narrow gap,, called the synaptic cleft, separates the pre-and subsynaptic membranes. Transmitters released from presynaptic nerve terminals diffuse across the synaptic cleft andd interact with receptors which are located at the subsynaptic membrane. The action of the transmitter is very rapid and powerful. The interaction of the transmitter with receptors results in the generation of a postsynaptic potential. The size of the postsynaptic potential is indicative of the efficiency of synaptic transmission. The postsynaptic potential (PSP) can be either an excitatory postsynaptic potential (EPSP) or an inhibitory postsynaptic potential (IPSP). When the EPSP depolarizes the postsynaptic membrane to a critical membrane potential, an action potential is produced which propagates along the membrane of the postsynaptic neurone.Such a typical transmission does not always occur. In many cases, a neurone which releases a transmitter does not make close contact with its target neurones. In general, endogenous substances, such as transmitters or hormones, reach the membranes of their target neurones via many different routes after they are released. Thus the actions of endogenous substances reaching remote target neurones should be relatively weak and slow, but sustained. This is different from the typical synaptic transmission. Furthermore, the mode of action of these substances may be more complex. The combination of these substances with their target receptors changes the physiological state of target neurones in a variety of ways. These actions of endogenous substances are considered to be modulatory on the target neurones.There appear to be at least four different types of modulatory actions by transmitters. In type 1 modulation, a transmitter acts on the membrane of a target neurone and changes the amount of transmitter or hormone released from the target neurone. Much research has been devoted to this type of modulatory action of transmitters, especially in connection with presynaptic inhibition. In type 2 modulation, the transmitter changes the sensitivity of a receptor located on

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Section: A) Experimental Evidencesupporting

confidence: 63%

Section: A) Experimental Evidencementioning

confidence: 99%

Modulation of receptor sensitivity and action potentials by transmitters in vertebrate neurones.

Koketsu

1984

Jpn.J.Physiol

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“…Therefore, the present results support a hypothesis that substance P may be a modulator of the sensitivity of the nicotinic receptor in cholinergic transmission. The present paper, together with recent reports on the action of 5-hydroxytryptamine (Akasu et al, 1981a), catecholamine (Koketsu et aL, 1982a, b, c) and adenosine triphosphate (Akasu et al, 1981b) provide important experimental evidence showing that the sensitivity of a receptor for its agonist can be modulated by the action of other neurotransmitters or neurohormones.…”

Section: Discussionmentioning

confidence: 97%

Substance P modulates the sensitivity of the nicotinic receptor in amphibian cholinergic transmission

Akasu

Kojima

Koketsu

1983

British J Pharmacology

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1 The effect of substance P on the sensitivity of nicotinic acetylcholine (ACh) receptors of bullfrog sympathetic ganglion cells and frog skeletal muscle endplate was examined electrophysiologically. 2 The amplitude of ACh-induced postsynaptic potential (ACh potential) and current (ACh current) were reversibly and dose-dependently reduced by substance P at low concentrations (0.42-42 AM).3 The mean amplitude of the miniature endplate potential (m.e.p.p.) was also reduced by substance P (4.2 pM).4 Substance P (4.2 tM) shifted the S-shaped dose-response curve of the ACh current downward. A Lineweaver-Burk plot constructed from the dose-response curve revealed that substance P depressed the maximum response ( V,,,) without changing the apparent affinity (Km) of ACh for the receptor.5 Substance P (0.42-42 1M) did not alter the reversal potential of the ACh current of the endplate. The half-decay time of endplate current (e.p.c.) and its voltage-dependency were not altered by substance P in these concentrations. 6 The depression of the ACh current by substance P may not be due to a blockade of the opened channel which has been activated by the preceding combination of ACh with the receptor. 7 These results suggest that substance P suppresses the sensitivity of nicotinic ACh-receptors of the sympathetic ganglion cell and skeletal muscle endplate, acting on a certain allosteric site but not the recognition site of ACh in the receptor-ionic channel complex.

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“…The op posite process is that of sensitization (Karczmar and Howard 1955;Karczmar 1957Karczmar , 1987 . Both processes are due to an allosteric receptor change (Akasu et al 1981); in the case of desensitization, this change may be medi ated by the activation of one or more kinases by a non cholinergic transmitter (Greengard 1987;see, however, Colquhoun et al 1990). …”

Section: Interactions Modulations and Gene Expressionmentioning

confidence: 99%

“…The term modulation, defined first by Kyo Ko ketsu, Les Blaber, and this author (Karczmar et al 1972;Karczmar 1990;Akasu et al 1981) Thesleff (1955) and Karczmar and Howard (1955) . The effect in question was desensitization or receptor inac tivation arising from prolonged application of depolar izers, including ACh, to the motor endplate .…”

Section: Interactions Modulations and Gene Expressionmentioning

confidence: 99%

Brief Presentation of the Story and Present Status of Studies of the Vertebrate Cholinergic System

Karczmar

1993

Neuropsychopharmacol

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This year marks the seventieth anniversary of Otto Loewi's demonstration of chemical transmission generally and autonomic cholinergic transmission specifically and the fortieth anniversary of John Eccles's proof of the existence of central cholinergic transmission. Following these epochal findings, the subsequent studies of the cholinergic system led to discoveries of similarly important phenomena. This review concerns these phenomena, including chemical structure and molecular biology of cholinergic receptors; electrophysiologic and ionic aspects of pre-and postsynaptic cholinergic events; the quantal expression of cholinergic postsynaptic events and activities of their subunits, the elementary events; and teratology; trophic phenomena; and the clinical aspects of the cholinergic system. This review refers to the history as well as the present status of each of these phenomena; furthermore, it describes briefly the nineteenth-century work with calabar bean, pilocarpine, muscarine, and nicotine, that is, the work performed before the promulgation of the cholinergic era.[ Neuropsychopharmacology 9:181-199, 1993J included the frrst descriptions of the trophic phenomena, the quantal nature of the biological events, the recep tors and their chemical structure, the role of a trans mittive system in arousal and memory, and so on. So, it is appropriate to sketch at this time the history and the present status of the vertebrate cholinergic studies.

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INCREASE OF ACETYLCHOLINE‐RECEPTOR SENSITIVITY BY ADENOSINE TRIPHOSPHATE: A NOVEL ACTION OF ATP ON ACh‐SENSITIVITY

Cited by 105 publications

References 4 publications

Modulation of receptor sensitivity and action potentials by transmitters in vertebrate neurones.

Modulation of receptor sensitivity and action potentials by transmitters in vertebrate neurones.

Substance P modulates the sensitivity of the nicotinic receptor in amphibian cholinergic transmission

Brief Presentation of the Story and Present Status of Studies of the Vertebrate Cholinergic System

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