6-cyano-7-nitroquinoxaline-2-3-dione and pyridoxal-phosphate-6-azophenyl-2--4--disulfonic-acid

Inhibitory GABAergic and glycinergic neurotransmission to cardioinhibitory cardiac vagal neurons (CVNs) increase during inspiratory activity and likely mediate respiratory sinus arrhythmia, while the frequency of excitatory postsynaptic currents (EPSCs) in CVNs are unaltered during the different phases of respiration. However, following hypoxia and hypercapnia (H/H), the parasympathetic activity to the heart increases and thus far, identification of the pathways and neurotransmitters that are responsible for exciting CVNs post H/H are unclear. This study identifies different excitatory pathways to CVNs recruited post H/H. Spontaneous and inspiratory-related EPSCs were recorded in CVNs before, during, and after 10 min of H/H in an in vitro slice preparation that retains rhythmic respiratory activity. Before and during H/H, EPSCs in CVNs were completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and d(-)-2-amino-5-phosphonopentanoic acid (AP5), selective AMPA/kainate and N-methyl-d-apartate (NMDA) receptor blockers, respectively. However, after H/H, there was a significant increase in EPSCs during each inspiratory burst. While some of the inspiratory-related EPSCs were blocked by the broad purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (PPADS) and the specific P2X receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate monolithium trisodium salt (TNP-ATP) a P2X receptor blocker, most of the recruited excitatory neurotransmission to CVNs is serotonergic because odansetron, a selective 5-HT3 antagonist, abolished the majority of the spontaneous and inspiratory-related EPSCs evoked during recovery from H/H. The results from this study suggest that following episodes of H/H, two nonglutamatergic excitatory pathways, purinergic and serotonergic, activating P2X and 5-HT3 receptors, respectively, are recruited to excite CVNs in the post H/H recovery period.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Animals; Animals, Newborn; Drug Interactions; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Hypercapnia; Hypoxia; In Vitro Techniques; Neurons; Nucleus Accumbens; Ondansetron; Patch-Clamp Techniques; Platelet Aggregation Inhibitors; Pyridoxal Phosphate; Rats; Rats, Sprague-Dawley; Respiration; Serotonin; Serotonin Antagonists; Vagus Nerve; Valine

Purinergic P2X receptors have been reported to be present in regions of the midbrain periaqueductal gray (PAG). The purpose of this study was to determine the role of presynaptic P2X receptors in modulating excitatory and inhibitory synaptic inputs to the dorsolateral PAG (dl-PAG), which has abundant neuronal connections. First, whole cell voltage-clamp recording was performed to obtain excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) of the dl-PAG neurons. Our data show that alpha, beta-methylene ATP (a P2X receptor agonist), in the concentration of 50 microM, significantly increased the frequency of miniature EPSCs without altering the amplitude of miniature EPSCs in eight tested neurons. The effects were attenuated by PPADS, an antagonist to P2X receptors. Furthermore, alpha, beta-methylene ATP increased the amplitude of evoked EPSCs, and decreased the paired-pulse ratio of eEPSCs in ten neurons. In contrast, activation of P2X had no distinct effect on IPSCs. In addition, immunofluorescent methods demonstrate that P2X labeling was co-localized with a presynaptic marker, synaptophysin, in the dl-PAG. The results of the current study provide the first evidence indicating that P2X receptors facilitate glutamatergic synaptic transmission in the dl-PAG via presynaptic mechanisms.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Analysis of Variance; Animals; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Female; Glutamic Acid; In Vitro Techniques; Male; Neurons; Patch-Clamp Techniques; Periaqueductal Gray; Platelet Aggregation Inhibitors; Presynaptic Terminals; Pyridoxal Phosphate; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2; Receptors, Purinergic P2X3; Synaptic Transmission; Synaptophysin

An extracellular nonsynaptic taurine pool of glial origin was recently reported in the substantia nigra (SN). There is previous evidence showing taurine as an inhibitory neurotransmitter in the SN, but the physiological role of this nonsynaptic pool of taurine has not been explored. By using microdialysis methods, we studied the action of local osmolarity on the nonsynaptic taurine pool in the SN of the rat. Hypoosmolar pulses (285-80 mosM) administered in the SN by the microdialysis probe increased extrasynaptic taurine in a dose-dependent way, a response that was counteracted by compensating osmolarity with choline. The opposite effect (taurine decrease) was observed when osmolarity was increased. Under basal conditions, the blockade of either the AMPA-kainate glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dionine disodium or the purinergic receptors with pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid modified the taurine concentration, suggesting that both receptors modulate the extrasynaptic pool of taurine. In addition, these drugs decreased the taurine response to hypoosmolar pulses, suggesting roles for glutamatergic and purinergic receptors in the taurine response to osmolarity. The participation of purinergic receptors was also supported by the fact that ATP (which, under basal conditions, increased the extrasynaptic taurine in a dose-dependent way) administered in doses saturating purinergic receptors also decreased the taurine response to hypoosmolarity. Taken together, present data suggest osmoregulation as a role of the nonsynaptic taurine pool of the SN, a function that also involves glutamate and ATP and that could influence the nigral cell vulnerability in Parkinson's disease.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Animals; Choline; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Glutamic Acid; Hypertonic Solutions; Hypotonic Solutions; Male; Microdialysis; Parkinson Disease; Purinergic P2 Receptor Antagonists; Pyridoxal Phosphate; Rats; Rats, Sprague-Dawley; Receptors, AMPA; Receptors, Purinergic P2; Substantia Nigra; Taurine; Time Factors; Water-Electrolyte Balance

ATP has been shown to excite neurons in various regions of the central nervous system. Whereas immunohistochemical studies show P2X receptors in the area postrema, the responsiveness of area postrema neurons to extracellular ATP has not been studied. To investigate the effects of purinoceptor activation on area postrema neuronal excitability, we performed whole-cell recordings from area postrema neurons in rat brain slices. Most area postrema neurons responded to ATP application, and most responses were excitatory. Voltage-clamp recordings showed three different types of response: (1) a postsynaptic or extrasynaptic excitatory response (inward currents; n=26/51 cells), (2) a presynaptic excitatory response (increased frequency of miniature excitatory postsynaptic currents with only a small direct postsynaptic current; n=24/51 cells, or (3) a postsynaptic inhibitory response (outward current; n=1/51). The excitatory responses were found in both of the two major electrophysiological cell classes, i.e. cells displaying I(h) and cells not displaying I(h), while the inhibitory responses were found in only cells not displaying I(h). Current-clamp recordings showed ATP-induced depolarization (n=13/15) or hyperpolarization (n=2/15) of membrane potential that modulated the frequency of action potentials. In the presence of CNQX, mEPSCs were abolished and bath-applied ATP did not generate mEPSCs, indicating that glutamate release was facilitated by the activation of presynaptically located ATP receptors. Our pharmacological results from studies with ATP, alphabetame-ATP, betame-ATP and PPADS indicate that the post- and/or extrasynaptic responses are most likely mediated by P2X(7) receptors and/or receptors composed of P2X(2) and P2X(5) subunits. We conclude that half of the presynaptic responses are most likely mediated by P2X(7) receptors and/or receptors composed of P2X(2) and P2X(5) subunits while the others also contain P2X(1) subunits. It is well known that P2X(7) subunit forms only homomultimeric P2X receptors. Finally, the present study suggests that purinoceptor activation may contribute to the control of several autonomic functions by area postrema neurons.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Anesthetics, Local; Animals; Animals, Newborn; Area Postrema; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation; Excitatory Amino Acid Antagonists; In Vitro Techniques; Neural Inhibition; Neurons; Patch-Clamp Techniques; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Pyridoxal Phosphate; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2; Receptors, Purinergic P2X; Tetrodotoxin

Hypocretin/orexin (hcrt) neurons play an important role in hypothalamic arousal and energy homeostasis. ATP may be released by neurons or glia or by pathological conditions. Here we studied the effect of extracellular ATP on hypocretin cells using whole cell patch-clamp recording in hypothalamic slices of transgenic mice expressing green fluorescent protein (GFP) exclusively in hcrt-producing cells. Local application of ATP induced a dose-dependent increase in spike frequency. In the presence of TTX, ATP (100 microM) depolarized the cells by 7.8 +/- 1.2 mV. In voltage clamp under blockade of synaptic activity with the GABA(A) receptor antagonist bicuculline, and ionotropic glutamate receptor antagonists DL-2-amino-5-phosphonopentanoic acid (AP-5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), ATP (100 microM) evoked an 18 pA inward current. The inward current was blocked by extracellular choline substitution for Na+, had a reversal potential of -27 mV, and was not affected by nominally Ca2+-free external buffer, suggesting that ATP activated a nonselective cation current. All excitatory effects of ATP showed rapid attenuation. ATP-induced excitatory actions were mimicked by nonhydrolyzable ATP-gamma-S but not by alpha,beta-MeATP and inhibited by the purinoceptor antagonists suramin and pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt (PPADS). The current was potentiated by a decrease in bath pH, suggesting P2X2 subunit involvement. Frequency and amplitude of spontaneous and miniature synaptic events were not altered by ATP. Suramin, but not PPADS, caused a small suppression of evoked excitatory synaptic potentials. Together, these results show a depolarizing response to extracellular ATP that would lead to an increased activity of the hypocretin arousal system.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Analysis of Variance; Animals; Bicuculline; Choline; Drug Interactions; Electric Stimulation; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; GABA Antagonists; Green Fluorescent Proteins; Hypothalamus; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; Membrane Potentials; Mice; Mice, Transgenic; Neurons; Neuropeptides; Orexin Receptors; Orexins; Patch-Clamp Techniques; Pyridoxal Phosphate; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Receptors, Purinergic P2; Receptors, Purinergic P2X2; Suramin; Tetrodotoxin

The effects of the P2 receptor ligands 2-methylthio ATP (2-MeSATP; 10 pmol)--as a non-specific agonist--and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10 pmol)--as a non-selective antagonist--after bilateral intra-accumbens injection on the locomotor response were investigated in an open field situation. The P2 receptor-mediated effects on the pattern of locomotor activity were compared with the effects caused by the dopamine D2-like receptor agonist quinpirole (10 pmol) and by the combination of the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 10 pmol) with the alpha-amino-3-hydro-5-methyl-4-isoxazolpropionic acid (AMPA) and kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 30 pmol). The intra-accumbens injection of all tested compounds elicited an increase in the locomotor activity over a test period of 20 min when compared with the controls. No statistically significant differences could be evaluated between the different drug-treated groups. However, a more detailed analysis--using further behavioural parameters such as the number of movement direction changes, the effective running time and the running speed--revealed two basically different patterns of locomotor activity. The locomotor response induced by the injection of 2-MeSATP or quinpirole was characterised by a continuous and consistent locomotion, whereas the enhanced locomotor activity elicited by PPADS or CPP/CNQX was determined by an increased running speed accompanied by more disruptions and more changes of movement direction. The coadministration of 2-MeSATP and quinpirole led to an enhancement of locomotor activity in a limited post-treatment interval. The effects of both compounds could be abolished by the pre-treatment with the D2/D3 receptor antagonist sulpiride (100 pmol). Coadministration of PPADS and CPP/CNQX caused additive effects suggesting that the pathway mediated by P2 and ionotrophic glutamate receptors is different. The stimulation of P2 receptors in the nucleus accumbens (NAc) modulates the locomotion in the direction to be to be longer lasting, more consistent and more goal directed.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Animals; Behavior, Animal; Dopamine Agonists; Dopamine Antagonists; Drug Interactions; Excitatory Amino Acid Antagonists; Locomotion; Male; Nucleus Accumbens; Piperazines; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Agonists; Pyridoxal Phosphate; Quinpirole; Rats; Rats, Wistar; Receptors, AMPA; Receptors, Dopamine D2; Receptors, Glutamate; Receptors, Purinergic P2; Sulpiride; Thionucleotides; Time Factors

Types and projections of neurons that received cholinergic, purinergic and other fast excitatory synaptic inputs in myenteric ganglia of the guinea-pig distal colon were identified using combined electrophysiological recording, application of selective antagonists, marker dye filling via the recording microelectrode, and immunohistochemical characterisation. Fast synaptic inputs were recorded from all major subtypes of uniaxonal neurons including Dogiel type I neurons, filamentous interneurons, circular muscle motor neurons and longitudinal muscle motor neurons. Fast excitatory postsynaptic potentials were completely blocked by the nicotinic receptor antagonists hexamethonium or mecamylamine in 62% of neurons tested and were partially inhibited in the remaining neurons. The P2 purine receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, reduced the amplitudes of fast excitatory postsynaptic potentials in 20% of myenteric neurons. The 5-hydroxytryptamine(3) receptor antagonist granisetron reduced the amplitude of fast excitatory postsynaptic potentials in only one of 15 neurons tested. In five of five neurons tested, the combination of a nicotinic antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid, granisetron and 6-cyano-7-nitroquinoxaline-2,3-dione did not completely block the fast excitatory postsynaptic potentials. Immunohistochemical studies of the neurons that had been identified electrophysiologically and morphologically imply that P2X(2) receptors may mediate fast transmission in some neurons, and that other P2X receptor subtypes may also be involved in fast synaptic transmission to myenteric neurons of the guinea-pig distal colon. Neurons with nicotinic and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid-sensitive fast excitatory postsynaptic potentials were present in both ascending and descending pathways in the distal colon. Thus, neither cholinergic nor mixed cholinergic/purinergic synaptic responses are confined to a particular class of neuron. The results indicate that acetylcholine and ATP are the major fast excitatory neurotransmitters in guinea-pig distal colon myenteric ganglia.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Animals; Colon; Coloring Agents; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Granisetron; Guinea Pigs; Myenteric Plexus; Neural Pathways; Neurons; Purinergic Antagonists; Pyridoxal Phosphate; Receptors, Nicotinic; Receptors, Purinergic; Serotonin Antagonists

1. In mechanically dissociated rat spinal cord substantia gelatinosa (SG) neurones attached with native presynaptic nerve endings, glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded using nystatin perforated patch recording mode under voltage-clamp conditions. Under these conditions, it was tested whether the changes in P2X receptor subtype on the glycinergic presynaptic nerve terminals occur during postnatal development. 2. ATP facilitated glycinergic mIPSC frequency in a concentration-dependent manner through all developmental stages tested, whereas alphabeta-methylene-ATP (alphabeta-me-ATP) was only effective at later developmental stages. 3. alphabeta-me-ATP-elicited mIPSC frequency facilitation was completely occluded in the Ca2+-free external solution, but it was not affected by adding 10(-4) M Cd2+. 4. alphabeta-me-ATP still facilitated mIPSC frequency even in the presence of 10(-6) M thapsigargin, a Ca2+ pump blocker. 5. In later developmental stages, ATP-elicited presynaptic or postsynaptic responses were reversibly blocked by 10(-5) M pyridoxal-5-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), but only partially blocked by 10(-7) M 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP). However, alphabeta-me-ATP-elicited presynaptic or postsynaptic responses were completely and reversibly blocked by either 10(-5) M PPADS or 10(-7) M TNP-ATP. 6. alphabeta-me-ATP significantly reduced the evoked glycinergic IPSC amplitude in postnatal 28-30 day neurones, whereas it had no effect in 10-12 day neurones. 7. It was concluded that alphabeta-me-ATP-sensitive P2X receptors were functionally expressed on the glycinergic presynaptic nerve terminals projecting to SG neurones in later developmental stages. Such developmental changes of presynaptic P2X receptor subtypes might contribute to synaptic plasticity such as the regulation of neuronal excitability and the fine controlling of the pain signal in spinal dorsal horn neurones.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Animals; Bicuculline; Excitatory Amino Acid Antagonists; Fluorescent Dyes; GABA Antagonists; Glycine; Membrane Potentials; Neural Inhibition; Neural Pathways; Neurons; Organ Culture Techniques; Patch-Clamp Techniques; Platelet Aggregation Inhibitors; Presynaptic Terminals; Pyridoxal Phosphate; Rats; Rats, Wistar; Receptors, Purinergic P2; Receptors, Purinergic P2X2; Receptors, Purinergic P2X4; Substantia Gelatinosa

Microdialysis experiments were used to investigate the influence of locally applied 2-methylthioadenosine 5'-triphosphate (2-MeSATP) on extracellular dopamine concentrations in the rat nucleus accumbens (NAc). 2-MeSATP (0.1, 1, 10 mM) infused via the microdialysis probe caused a concentration-dependent stimulation of dopamine release. The P2 receptor antagonists reactive blue 2 and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (30 microM each) depressed the basal release of dopamine when given alone and in addition counteracted the stimulatory effect of 2-MeSATP (1 mM). In contrast, a combination of the excitatory amino acid receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 300 microM) and 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 100 microM) increased the basal release of dopamine by themselves and facilitated the effect of 2-MeSATP (1 mM). The results suggest a physiologically relevant regulation of tonic dopamine release in the NAc by endogenous ATP via P2 receptors. This is due to the combination of a direct and an indirect (via glutamate release) effect of ATP on mesolimbic dopaminergic neurons.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Analysis of Variance; Animals; Dopamine; Excitatory Amino Acid Antagonists; Male; Microdialysis; Nucleus Accumbens; Piperazines; Purinergic P2 Receptor Antagonists; Pyridoxal Phosphate; Rats; Rats, Wistar; Thionucleotides; Triazines

The pyramidal neurons in the CA1 area of hippocampal slices from 17- to 19-day-old rats have been investigated by means of patch clamp. Excitatory postsynaptic currents (EPSCs) were elicited by stimulating the Schaffer collateral at a frequency below 0.2 Hz. It was found that inhibition of glutamatergic transmission by 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 100 microM 2-amino-5-phosphonovaleric acid (D-APV) left a small component of the EPSC uninhibited. The amplitude of this residual EPSC (rEPSC) comprised 25 +/- 11% of the total EPSC when measured at a holding potential of -50 mV. The rEPSC was blocked by selective P2 blocker pyridoxal phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) 10 microM and bath incubation with non-hydrolysable ATP analogues, ATP-gamma-S and alpha, beta-methylene-ATP at 50 and 20 microM, respectively. The rEPSC was dramatically potentiated by external Zn2+ (10 microM). In another series of experiments exogenous ATP was applied to the CA1 neurons in situ. An inward current evoked by ATP was inhibited by PPADS to the same extent as the rEPSC. It is concluded that, depending on membrane voltage, about one-fifth to one-quarter of the EPSC generated by the excitatory synaptic input to the hippocampal CA1 neurons of rat is due to the activity of P2X receptors.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; Animals; Electrophysiology; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Glutamic Acid; Hippocampus; Neurons; Organ Culture Techniques; Platelet Aggregation Inhibitors; Pyridoxal Phosphate; Rats; Rats, Wistar; Receptors, Purinergic P2; Receptors, Purinergic P2X2; Receptors, Purinergic P2X4; Stimulation, Chemical

1. Intracellular recordings were made in a pontine slice preparation of the rat brain containing the nucleus locus coeruleus (LC). The pressure application of alpha,beta-methylene ATP (alpha,beta-meATP) caused reproducible depolarizations which were depressed by suramin (30 microM) and abolished by suramin (100 microM). Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10, 30 microM) also concentration-dependently inhibited the alpha,beta-meATP-induced depolarization, although with a much slower time-course than suramin. Almost complete inhibition developed with 30 microM PPADS. Reactive blue 2 (30 microM) did not alter the effect of alpha,beta-meATP, while reactive blue 2 (100 microM) slightly depressed it. 2. Pressure-applied (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) also depolarized LC neurones. Kynurenic acid (500 microM) depressed and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM) abolished the response to AMPA. Suramin (100 microM) potentiated the AMPA effect. 3. Pressure-applied noradrenaline hyperpolarized LC neurones. Suramin (100 microM) did not alter the effect of noradrenaline. 4. Focal electrical stimulation evoked biphasic synaptic potentials consisting of a fast depolarization (p.s.p.) followed by a slow hyperpolarization (i.p.s.p.). A mixture of D(-)-2-amino-5-phosphonopentanoic acid (AP-5; 50 microM), CNQX (50 microM) and picrotoxin (100 microM) depressed both the p.s.p. and the i.p.s.p. Under these conditions suramin (100 microM) markedly inhibited the p.s.p., but did not alter the i.p.s.p. In the combined presence of AP-5 (50 microM), CNQX (50 microM), picrotoxin (100 microM), strychnine (0.1 microM), tropisetron (0.5 microM) and hexamethonium (100 microM), a high concentration of suramin (300 microM) almost abolished the p.s.p. without changing the i.p.s.p. 5. In the presence of kynurenic acid (500 microM) and picrotoxin (100 microM), PPADS (30 microM) depressed the p.s.p. Moreover, the application of suramin (100 microM) to the PPADS (30 microM)-containing medium failed to cause any further inhibition. Neither PPADS (30 microM) nor suramin (100 microM) altered the i.p.s.p. 6. It was concluded that the cell somata of LC neurones are endowed with excitatory P2-purinoceptors. ATP may be released either as the sole transmitter from purinergic neurones terminating at the LC or as a co-transmitter of noradrenaline from recurrent axon collaterals or dendrites of the LC neurones themselves.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adenosine Triphosphate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Electric Stimulation; Excitatory Amino Acid Agonists; Excitatory Postsynaptic Potentials; GABA Antagonists; In Vitro Techniques; Kynurenic Acid; Locus Coeruleus; Male; Picrotoxin; Purinergic P2 Receptor Antagonists; Pyridoxal Phosphate; Rats; Rats, Wistar; Receptors, Purinergic P2; Suramin