The actions of adenosine 5′‐triphosphate on guinea‐pig intracardiac neurones in culture

Allen, T. G. J.; Burnstock, Geoffrey

doi:10.1111/j.1476-5381.1990.tb15794.x

Cited by 61 publications

(42 citation statements)

References 40 publications

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“…Outside of the CNS, purinoceptor mediated responses have been detected with a profile of agonist potency similar to that of P2X 4 [27]. P2X 4 message was found to be widely expressed throughout many different tissues; thus the P2X4 subtype appears to be the most widespread member of the P2X family.…”

Section: Discussionmentioning

confidence: 89%

A P2X purinoceptor cDNA conferring a novel pharmacological profile

et al. 1995

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We have cloned P2X4, a member of the P2-purinoceptor family, which has a new pharmacological profile. Rat P2X 4 is distantly related to P2XI, P2X2 and P2X 3 and is expressed in brain, spinal cord, lung, thymus, bladder, adrenal, testis and vas deferens. This ligand gated ion channel is activated by ATP and analogs with the potency order ofATP > ATP3,S > 2-methylthio ATP > ADP = ai~-methylene ATP. However, none of the currently used P2X purinoceptor antagonists suramin, reactive blue 2 and PPADS blocked ATP evoked currents; in contrast their application resulted in potentiation of the agonist response. Due to lack of any known antagonist for P2X 4 it is unlikely that native P2X 4 has previously been recognized as a P2X purinoceptor.

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Section: Discussionmentioning

confidence: 89%

A P2X purinoceptor cDNA conferring a novel pharmacological profile

et al. 1995

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“…Although several other workers have shown that ATP excites neurones grown in culture from parasympathetic cardiac ganglia (Allen & Burnstock, 1990;Fieber & Adams, 1991) and nodose ganglia (Krishtal et al, 1988a,b) this is, as far as we know, the first demonstration of a depolarizing effect of this agent on whole vagal nerve trunks. The depolarizing action of ATP was marked but high concentrations were necessary.…”

Section: Discussionmentioning

confidence: 97%

“…From the relative order of potencies of a series of ATP analogues, the predominant effect is mediated by a receptor which appears to be a P2X, receptor. Interestingly, from patch-and voltage-clamp studies on neurones cultured from parasympathetic intracardiac ganglia it appears that the excitatory effects of purines are mediated via a receptor that shares more similarities with the P2y than the P2, purinoceptor (Allen & Burnstock, 1990;Fieber & Adams, 1991). It remains to be established whether there is a genuine difference in the purine receptor population on the intracardiac neurones and on the axonal membranes of the cervical vagal nerve trunk or whether these contrasting findings can be attributed to the different methods used to study these receptors.…”

Section: Discussionmentioning

confidence: 99%

“…For example, structure-function relationships for purine nucleotideevoked depolarization of rat cultured nodose ganglion neurones have been described (Krishtal et al, 1988b) although no attempt was made to classify the receptor type(s) mediating this effect. In bullfrog dorsal root ganglion cells and rat and guinea-pig cardiac ganglia, membrane depolarization evoked by ATP is mediated via a P2 purinoceptor which resembles the P2y receptor (Allen & Burnstock, 1990;Tokimasa & Akasu, 1990;Fieber & Adams, 1991). In contrast, the purinoceptor that mediates excitation of neurones in the rat locus coeruleus paradoxically shares characteristics of both the P2, and the P2y receptor Tsch6pl et al, 1992; but see Illes & Norenberg, 1993).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of purinoceptors mediating depolarization of rat isolated vagus nerve

Trezise

Kennedy

Humphrey

1993

British J Pharmacology

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1 As part of a broader study to characterize neuronal purinoceptors, the effects of adenosine 5'-triphosphate (ATP) and a range of ATP analogues were investigated on the extracellularly recorded membrane potential of the rat isolated vagus nerve, using a 'grease-gap' technique. 2 ATP evoked depolarization of the rat vagus nerve. The concentration-effect curve to ATP was not monophasic: at the lower concentrations (1 x I0-'-1 x I0-3M) the curve was shallow (<50% of the near maximal response to 5-hydroxytryptamine (5-HT)) whilst at higher concentrations the relationship between concentration and amplitude of depolarization was steeper (> 135% of the response to 5-HT at the highest concentration tested, 1 x 102 M). On washout of the high drug concentrations large after-hyperpolarizations were often observed.3 a,-methylene ATP (1 x 10-6-3 x 10-4 M), P,Iy-methylene ATP (1 x 10-6_ 1 x I0-3 M), and 5'-adenylylimidodiphosphate (P,T-imido ATP; 1 X 10-6 1 x 10-3M) were all more potent than ATP and produced large depolarizations of the rat vagus nerve at the highest concentrations tested (> 150% of the response to 5-HT). The overall rank order of potency was a,-methylene ATP> P,Ty-methylene ATP = P,-imido ATP> ATP. 4 In contrast, 2-methylthio ATP (1 X 10-6 1 X 1O-3 M) produced relatively small depolarizations (< 100% of the response to 5-HT). As was the case with low concentrations of ATP, the concentrationeffect curve to 2-methylthio ATP was very shallow. 5 Adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), adenosine and adenosine 5'-O-(2-thiodiphosphate) (ADP-,-s; all 1 x 10-6 1 x 1O-3M) evoked only small depolarizations of the vagus nerve, amounting to 47 ± 2.5%, 40.8 ± 7.8%, 33.7 ± 3.3% and 62.4 ± 12.7% of the response to 5-HT, respectively. Uridine 5'-triphosphate (UTP; 1 X 10-6 1 X 10-3M) was inactive.6 The P2 purinoceptor antagonist, suramin (1 x 10-SM-_1 X 10-4 M), antagonized responses to x4j-methylene ATP. The nature of this antagonism was not, however, consistent with simple competitive kinetics between agonist and antagonist. Depolarizations produced by P,y-methylene ATP and ,-imido ATP were also attenuated by suramin (1 x 10-4 M), but in contrast, suramin had no effect on responses to ADP, 2-methylthio ATP, ADP-P-S or 5-HT.7 In addition to its antagonist effects, suramin (10-4 M) markedly increased the maximum amplitude of the depolarization produced by ATP. 8 It is concluded that a heterogeneous receptor population mediates depolarization of the rat vagus nerve by purine nucleotides. Importantly, the large amplitude depolarizations to a,p-methylene ATP, P,y-methylene ATP and P,y-imido ATP are mediated via receptors that share many characteristics of the classical P2, receptor. In contrast, the relatively small depolarizing effects of ADP, ADP-1B-S and 2-methylthio ATP were suramin-resistant. Although it appears that other purinoceptors are present, these data suggest that the rat vagus nerve may serve as a useful preparation for studying the pharmacology of neuronal P2, receptors.

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“…These currents were, however, insensitive to the muscarinic receptor antagonists, pirenzepine and atropine (data not shown) and thus constitute a nicotinic AChR-mediated current. An ATP-induced current has also been described in parasympathetic neurones of mammalian intracarditc ganglia (Allen & Burnstock, 1990b;Fieber & Adams, 1991b)`i However, ATP-evoked currents were unaffected Ity bath application of either 1I00 jiM potential. This voltage sensitivity suggests that QX-222 binds at a site within the electric field, presumably the pore-forming region, of the ACh receptor-channel in parasympathetic neurones.…”

Section: Single-channel Recordingsmentioning

confidence: 99%

Local anaesthetic blockade of neuronal nicotinic ACh receptor‐channels in rat parasympathetic ganglion cells

Cuevas

Adams

1994

British J Pharmacology

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1 The effects of the local anaesthetics QX-222 and procaine on nicotinic acetylcholine (ACh)-evoked currents in cultured parasympathetic cardiac neurones of the rat were investigated by use of the whole-cell, perforated-patch, and outside-out recording configurations of the patch clamp method. 2 QX-222 and procaine, applied to the extracellular surface, reversibly inhibited the peak amplitude of the whole-cell nicotinic ACh-evoked current in a concentration-dependent manner, with half-maximal inhibitory concentrations (IC50) of 28 pM and 2.8 pLM, respectively, at -80 mV. In these neurones, the sustained inward current mediated by Ml muscarinic receptor activation was unaltered by QX-222, and neither local anaesthetic affected the adenosine 5'-triphosphate (ATP)-evoked current. 3 QX-222 and procaine block of nicotinic ACh-evoked inward current was voltage-dependent and enhanced by hyperpolarization. An e-fold change in their dissociation equilibrium constants (Kd) resulted from a 62 mV and a 122 mV change in membrane potential, respectively. 4 Both local anaesthetics produce a concentration-dependent increase in the half-time of decay of the nicotinic ACh-evoked inward current. 5 Measurements of unitary currents in outside-out patches showed that QX-222 reversibly increased the mean burst duration and closed time and reduced the mean channel open time and open-state probability of the nicotinic ACh receptor-channel (AChR) in a concentration-dependent manner. 6 The Kd and voltage sensitivity of local anaesthetic block of the nicotinic AChR in rat intracardiac neurones suggests that the pore-forming region of this channel differs from that of the AChR in frog and rat skeletal muscle and from the neuronal a42 ACh receptor-channel.

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The actions of adenosine 5′‐triphosphate on guinea‐pig intracardiac neurones in culture

Cited by 61 publications

References 40 publications

A P2X purinoceptor cDNA conferring a novel pharmacological profile

A P2X purinoceptor cDNA conferring a novel pharmacological profile

Characterization of purinoceptors mediating depolarization of rat isolated vagus nerve

Local anaesthetic blockade of neuronal nicotinic ACh receptor‐channels in rat parasympathetic ganglion cells

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