Characterization of a P2X-purinoceptor in cultured neurones of the rat dorsal root ganglia. 1996

S J Robertson, and M G Rae, and E G Rowan, and C Kennedy
Department of Physiology and Pharmacology, University of Strathelyde, Royal College, Glasgow.

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.

UI MeSH Term Description Entries
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005727 Ganglia, Spinal Sensory ganglia located on the dorsal spinal roots within the vertebral column. The spinal ganglion cells are pseudounipolar. The single primary branch bifurcates sending a peripheral process to carry sensory information from the periphery and a central branch which relays that information to the spinal cord or brain. Dorsal Root Ganglia,Spinal Ganglia,Dorsal Root Ganglion,Ganglion, Spinal,Ganglia, Dorsal Root,Ganglion, Dorsal Root,Spinal Ganglion
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013498 Suramin A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. Germanin,Moranil,Naganin,Naganol,Naphuride,Suramin Sodium,Suramin, Hexasodium Salt,Suramin, Monosodium Salt,Hexasodium Salt Suramin,Monosodium Salt Suramin,Salt Suramin, Hexasodium,Salt Suramin, Monosodium,Sodium, Suramin
D014544 Uridine Triphosphate Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety. UTP,Magnesium UTP,Magnesium Uridine Triphosphate,Mg-UTP,Mg UTP,Triphosphate, Magnesium Uridine,Triphosphate, Uridine,UTP, Magnesium
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D058919 Purinergic P2 Receptor Antagonists Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS. P2 Purinoceptor Antagonists,P2 Purinoceptor Blockers,Purinergic P2 Receptor Blockers,Antagonists, P2 Purinoceptor,Blockers, P2 Purinoceptor,Purinoceptor Antagonists, P2,Purinoceptor Blockers, P2

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