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Characterization of a P2X-purinoceptor in cultured neurones of the rat dorsal root ganglia.
Br J Pharmacol 1996; 118(4):951-6BJ

Abstract

1. The electrophysiological actions of the P2-purinoceptor agonists, adenosine 5'-triphosphate (ATP), 2-methylthio ATP (2-meSATP) and alpha, beta-methyleneATP (alpha, beta-meATP) and of uridine 5'-triphosphate (UTP) were studied under concentration and voltage-clamp conditions in dissociated neurones of 1-6 day old rat dorsal root ganglia. 2. ATP (10 nM-100 microM) applied rapidly via a U-tube perfusion system (equilibration time < 10 ms) activated concentration-dependent inward currents with a latency to onset of a few ms, an EC50 of 719 nM and a Hill slope of 1.47. 3. 2-meSATP (10 nM- 100 microM) and alpha, beta-meATP (100 nM - 100 microM) also evoked transient inward currents. The EC50 and Hill slopes were 450 nM and 1.58 for 2-meSATP and 1.95 microM and 1.53 for alpha, beta-meATP respectively. There was no significant difference between the maximum currents evoked by the three agonists. 4. As the concentration of ATP increased so the rate of rise and decay of the currents also increased. At 100 and 300 nM ATP the decay of the current was best fitted by a single exponential, but at 1 microM and above two exponentials were required. Log-log plots of the rise time or time constants of decay versus concentration were linear. Currents evoked by 2-meSATP and alpha, beta-meATP showed a similar concentration-dependence in their kinetics. 5. Inward currents evoked by ATP, 2-meSATP and alpha, beta-meATP (300 nM) were abolished by the P2-purinoceptor antagonist, suramin (100 microM). 6. UTP (10 microM) evoked similar transient inward currents, which were sensitive to suramin (100 microM). ATP (10 microM), applied 2 min beforehand, reduced the response to UTP (10 microM) by 80 +/- 10%. 7. This study shows that ATP, 2-meSATP and alpha, beta-meATP act via a suramin-sensitive P2x-purinoceptor to evoke rapid, transient inward currents in dissociated neurones of rat dorsal root ganglia. The pyrimidine nucleotide, UTP, was also active. It is likely that the agonists were acting at the P2x3-subtype to produce these effects.

Authors+Show Affiliations

Department of Physiology and Pharmacology, University of Strathelyde, Royal College, Glasgow.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8799567

Citation

Robertson, S J., et al. "Characterization of a P2X-purinoceptor in Cultured Neurones of the Rat Dorsal Root Ganglia." British Journal of Pharmacology, vol. 118, no. 4, 1996, pp. 951-6.
Robertson SJ, Rae MG, Rowan EG, et al. Characterization of a P2X-purinoceptor in cultured neurones of the rat dorsal root ganglia. Br J Pharmacol. 1996;118(4):951-6.
Robertson, S. J., Rae, M. G., Rowan, E. G., & Kennedy, C. (1996). Characterization of a P2X-purinoceptor in cultured neurones of the rat dorsal root ganglia. British Journal of Pharmacology, 118(4), pp. 951-6.
Robertson SJ, et al. Characterization of a P2X-purinoceptor in Cultured Neurones of the Rat Dorsal Root Ganglia. Br J Pharmacol. 1996;118(4):951-6. PubMed PMID: 8799567.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of a P2X-purinoceptor in cultured neurones of the rat dorsal root ganglia. AU - Robertson,S J, AU - Rae,M G, AU - Rowan,E G, AU - Kennedy,C, PY - 1996/6/1/pubmed PY - 1996/6/1/medline PY - 1996/6/1/entrez SP - 951 EP - 6 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 118 IS - 4 N2 - 1. The electrophysiological actions of the P2-purinoceptor agonists, adenosine 5'-triphosphate (ATP), 2-methylthio ATP (2-meSATP) and alpha, beta-methyleneATP (alpha, beta-meATP) and of uridine 5'-triphosphate (UTP) were studied under concentration and voltage-clamp conditions in dissociated neurones of 1-6 day old rat dorsal root ganglia. 2. ATP (10 nM-100 microM) applied rapidly via a U-tube perfusion system (equilibration time < 10 ms) activated concentration-dependent inward currents with a latency to onset of a few ms, an EC50 of 719 nM and a Hill slope of 1.47. 3. 2-meSATP (10 nM- 100 microM) and alpha, beta-meATP (100 nM - 100 microM) also evoked transient inward currents. The EC50 and Hill slopes were 450 nM and 1.58 for 2-meSATP and 1.95 microM and 1.53 for alpha, beta-meATP respectively. There was no significant difference between the maximum currents evoked by the three agonists. 4. As the concentration of ATP increased so the rate of rise and decay of the currents also increased. At 100 and 300 nM ATP the decay of the current was best fitted by a single exponential, but at 1 microM and above two exponentials were required. Log-log plots of the rise time or time constants of decay versus concentration were linear. Currents evoked by 2-meSATP and alpha, beta-meATP showed a similar concentration-dependence in their kinetics. 5. Inward currents evoked by ATP, 2-meSATP and alpha, beta-meATP (300 nM) were abolished by the P2-purinoceptor antagonist, suramin (100 microM). 6. UTP (10 microM) evoked similar transient inward currents, which were sensitive to suramin (100 microM). ATP (10 microM), applied 2 min beforehand, reduced the response to UTP (10 microM) by 80 +/- 10%. 7. This study shows that ATP, 2-meSATP and alpha, beta-meATP act via a suramin-sensitive P2x-purinoceptor to evoke rapid, transient inward currents in dissociated neurones of rat dorsal root ganglia. The pyrimidine nucleotide, UTP, was also active. It is likely that the agonists were acting at the P2x3-subtype to produce these effects. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/8799567/Characterization_of_a_P2X_purinoceptor_in_cultured_neurones_of_the_rat_dorsal_root_ganglia_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&amp;sid=nlm:pubmed&amp;issn=0007-1188&amp;date=1996&amp;volume=118&amp;issue=4&amp;spage=951 DB - PRIME DP - Unbound Medicine ER -