PD 116,948, a highly selective A1 adenosine receptor antagonist

Haleen, Stephen J.; Steffen, Robert P.; Hamilton, Harriet W.

doi:10.1016/0024-3205(87)90369-9

Cited by 84 publications

(42 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(Haleen, Steffen & Hamilton, 1987). In five cells we found that 40 /M adenosine failed to activate a K+ current when it was applied in the presence of 1 juM DPCPX, though they responded to adenosine in its absence.…”

Section: Charybdotoxin and Apaminmentioning

confidence: 74%

Adenosine‐activated potassium current in smooth muscle cells isolated from the pig coronary artery.

Dart

Standen

1993

The Journal of Physiology

180

132

View full text Add to dashboard Cite

SUMMARY1. The perforated patch technique with nystatin or amphotericin was used to record whole cell currents activated by adenosine in smooth muscle cells isolated enzymatically from pig coronary arteries.2. Adenosine (5-40 /SM) activated an outward current at a holding potential of 0 mV in 5 mm [K+]. and an inward current at -60 mV in 143 mm [K+] Openings became more frequent after the application of adenosine, with several levels then being detected. Openings of channels with a larger conductance were sometimes also seen in the presence of adenosine. Fluctuation analysis gave somewhat lower estimates of unitary current than did direct measurements.5. The effect of adenosine could be mimicked by the A1 receptor agonist CCPA (2-chloro-NM-cyclopentyladenosine), while the A2 agonist CGS 21680 (2-p-(2-carboxethyl)phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride) was without effect. The response to adenosine was inhibited by the A, antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine), but was unaffected by the A2antagonist CGS 15943A (5-amino-9-chloro-2-(2-furanyl)-1,2,4-triazolo[1,5-C]quinazoline monomethanesulphonate). 6. Our results suggest that adenosine acts at an A1 receptor to activate K+ channels. We consider it most likely that these are ATP-dependent K+ channels. We discuss the mechanism by which K+ channel activation may lead to hyperpolarization and so vasorelaxation.

show abstract

Section: Charybdotoxin and Apaminmentioning

confidence: 74%

Adenosine‐activated potassium current in smooth muscle cells isolated from the pig coronary artery.

Dart

Standen

1993

The Journal of Physiology

180

132

View full text Add to dashboard Cite

show abstract

“…That the contraction in RCMM is mediated via adenosine Al receptors was further substantiated by the effect of DPCPX, an Al-selective antagonist (Bruns et al, 1987;Haleen et al, 1987). DPCPX produced concentrationdependent, rightward displacements of the NECA concentration-effect curves and mean pKB values of approximately 9.2 were calculated.…”

Section: Discussionmentioning

confidence: 88%

Characterization of the adenosine receptor mediating contraction in rat colonic muscularis mucosae

Reeves¹,

Coates²,

Jarvis³

et al. 1993

British J Pharmacology

View full text Add to dashboard Cite

1 The objective of this study was to characterize the adenosine receptor mediating contraction in rat isolated colonic muscularis mucosae (RCMM). 2 Sequential additions of the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA; 0.01 -10 gM) elicited reproducible, concentration-related contractions in RCMM. The effects of NECA were mimicked by the adenosine Al receptor-selective agonists cyclopentyladenosine (CPA), Rphenylisopropyladenosine (R-PIA) and N-[1S, trans)2-hydroxycyclopentyl] adenosine (GR79236) and by S-PIA (the stereoisomer of R-PIA). The adenosine A2 agonists N-[(2-methylphenyl)methyl] adenosine (metrifudil) and 2-[p-(2-carboxyethyl)phenethylamine]-5'-N-ethylcarboxamidoadenosine (CGS21680) also produced contractions in RCMM but were 54 and 165 times less potent respectively than NECA. The rank order of agonist potency for contraction of RCMM was CPA > GR79236 = R-PIA ) NECA> >S-PIA = metrifudil > CGS21680, which is identical to that reported for the inhibition of spontaneous rate in rat isolated right atria and inhibition of lipolysis in rat isolated adipocytes by these same agonists. 3 R-PIA, S-PIA and metrifudil behaved as partial agonists in RCMM. 5 The contractile responses to NECA in RCMM were not affected by atropine (1 JiM), tetrodotoxin (0.3 JAM) or the P2 antagonist, suramin (100IM). 6 The present study confirms that contractions to adenosine agonists in the RCMM are mediated via adenosine Al receptors.

show abstract

“…To preclude endogenous G-protein-mediated modulation during trains of stimuli, the GABA B receptor antagonist CGP55845a (2 M) (Davies et al, 1993), the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPC PX) (5 M) (Haleen et al, 1987), and the mGlu-RIII antagonist ( RS)-␣-cyclopropyl-4-phosphonophenylglycine (C PPG) (30 M) (Jane et al, 1996) were included in the external saline. These antagonists had no effect on EPSC amplitudes during low-frequency stimulation (Ͻ0.1 Hz) (n ϭ 3; data not shown).…”

Section: Methodsmentioning

confidence: 99%

Modulation of Transmission during Trains at a Cerebellar Synapse

Kreitzer

Regehr

2000

J. Neurosci.

View full text Add to dashboard Cite

Activity-dependent processes dynamically regulate synapses on the time scale of milliseconds to seconds. Here, we examine the factors governing synaptic strength during repetitive stimulation, both in control conditions and during presynaptic inhibition. Field recordings of presynaptic volleys, optical measurements of presynaptic calcium, and voltage-clamp recordings of postsynaptic currents were used to examine parallel fiber to Purkinje cell synapses in cerebellar brain slices at 34°C. In control conditions, regular stimulus trains (1-50 Hz) evoked up to a 250% peak synaptic enhancement, whereas during irregular stimulation, a threefold variability in EPSC amplitude was observed. When initial EPSC amplitudes were reduced by 50%, either by lowering external calcium or by activating adenosine A 1 or GABA B receptors, the peak enhancement during regular trains was 500%, and synaptic variability during irregular trains was nearly sixfold. By contrast, changes in fiber excitability and calcium influx per pulse were small during trains. Presynaptic calcium measurements indicated that by pulse 10, stimulusevoked calcium influx had increased by ϳ15%, which on the basis of the measured relationship between calcium influx and release corresponds to an EPSC enhancement of 50%. This enhancement was the same in all experimental conditions, even in the presence of N 6 -cyclopentyladenosine or baclofen, suggesting that repetitive stimulation does not relieve the G-protein inhibition of calcium channels by these modulators. Therefore, for our experimental conditions, changes in synaptic strength during trains are primarily attributable to residual calcium (Ca res )-dependent short-term plasticities, and the actions of neuromodulators during repetitive stimulation result from their inhibition of initial calcium influx and the resulting effects on Ca res and calcium-driven processes.

show abstract

PD 116,948, a highly selective A1 adenosine receptor antagonist

Cited by 84 publications

References 4 publications

Adenosine‐activated potassium current in smooth muscle cells isolated from the pig coronary artery.

Adenosine‐activated potassium current in smooth muscle cells isolated from the pig coronary artery.

Characterization of the adenosine receptor mediating contraction in rat colonic muscularis mucosae

Modulation of Transmission during Trains at a Cerebellar Synapse

Contact Info

Product

Resources

About