Role of action potentials and calcium influx in ATP- and UDP-induced noradrenaline release from rat cultured sympathetic neurones

Kügelgen, Ivar von; Nörenberg, Wolfgang; Meyer, Angelika; Illéš, Peter; Starke, Klaus

doi:10.1007/pl00005362

Cited by 31 publications

(35 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The evoked increase in calcium concentration was also markedly affected by -conotoxin GVIA, but not by nifedipine or -agatoxin IVa, indicating that the increase was at least predominantly mediated by an influx of calcium ions through N-type (Ca v 2.2; Ertel et al, 2000) calcium channels (for references, see above). N-type calcium channels also play the predominant role in stimulation-evoked calcium entry in postganglionic sympathetic neurons (e.g., Hirning et al, 1988;von Kü gelgen et al, 1999b). In contrast, in adrenal chromaffin cells and cell bodies of PC12 cells, L-type and P/Q-type channels are involved in addition to the N-type channels in the evoked entry of calcium (Liu et al, 1996;Lukyanetz and Neher, 1999).…”

Section: Discussionmentioning

confidence: 99%

P2Y-Receptors Mediating an Inhibition of the Evoked Entry of Calcium through N-Type Calcium Channels at Neuronal Processes

Kulick¹,

Kügelgen²

2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

In the search for P2-receptors modulating the stimulation-evoked entry of calcium at processes of PC12 cells differentiated in the presence of nerve growth factor and neurotrophin-3, electrically evoked increases in free calcium were assessed by fura-2 microfluorimetry. Omission of calcium and addition of cadmium (100 M) or the N-type calcium channel blocker -conotoxin GVIA (0.5 M) abolished or markedly reduced the evoked responses. The P2Y-receptor agonists 2-methylthio adenosine 5Ј-diphosphate (2-methylthio-ADP), ADP, and adenosine 5Ј-O-(2-thiodiphosphate) (ADP␤S) inhibited the electrically evoked entry of calcium without any changes in basal calcium concentrations. 2-Methylthio-ADP was the most potent agonist. Adenosine, P -methyl-2Ј-deoxyadenosine 3Ј,5Ј-bisphosphate; 10 M), as well as the adenosine A 1 -receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine; 100 nM), caused no change. Pretreatment with pertussis toxin abolished the effect of ADP␤S. Reverse transcriptase-polymerase chain reaction revealed the presence of mRNA for P2Y12-receptors in nondifferentiated and differentiated PC12 cells. The results indicate that processes of differentiated PC12 cells possess P2Y12-receptors coupling to pertussis toxin-sensitive G-proteins and mediating an inhibition of the stimulation-evoked entry of calcium through -conotoxin GVIA-sensitive calcium channels. This suggests a role of P2Y12-receptors in neuromodulation in addition to their involvement in platelet aggregation.The operation of P2-receptors inhibiting the release of neurotransmitters has been demonstrated in the peripheral and central nervous system (for reviews see Silinsky et al., 1998;Inoue et al., 1999;von Kü gelgen et al., 1999a). At postganglionic sympathetic axons the receptors are activated by endogenous adenine nucleotides released as cotransmitters of norepinephrine and, hence, mediate a negative feedback inhibition of sympathetic transmitter release (Fuder and Muth, 1993;von Kü gelgen et al., 1993). Release-inhibiting P2-receptors have also been found in adrenal chromaffin cells and the cell bodies of rat PC12 cells (Gandia et al., 1993;Currie and Fox, 1996;Powell et al., 2000;Vartian and Boehm, 2001;Unterberger et al., 2002). The release-inhibiting P2-receptors share some properties with cloned and expressed P2Y1-receptors (for references see above), but their molecular identity is yet not known. In addition to inhibitory P2-receptors, the cell bodies of postganglionic sympathetic neurons, adrenal chromaffin cells, and PC12 cells possess excitatory P2-receptors of distinct subtypes and with distinct signaling transduction pathways (for reviews see Silinsky et al., 1998;von Kü gelgen et al., 1999a; for PC12 cells see, for example, Arslan et al., 2000;Unterberger et al., 2002).The inhibition of calcium channels at axon terminals is a key element in the modulation of transmitter release by inhibitory G-protein-coupled receptors (see Przywara et al., 1993;Mirotznik et al., 2000;Jarvis and Zamponi, 2001). Therefore, we searched for...

show abstract

Section: Discussionmentioning

confidence: 99%

P2Y-Receptors Mediating an Inhibition of the Evoked Entry of Calcium through N-Type Calcium Channels at Neuronal Processes

Kulick¹,

Kügelgen²

2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…In rat superior cervical ganglion cells, ATP evokes inward currents (73,233,324,327,386,387) and elicits the release of norepinephrine (30,487). Rogers and Dani (387) measured directly the calcium permeability of the P2X receptors by simultaneous measurements of intracellular calcium and membrane currents.…”

Section: Sympathetic Neuronsmentioning

confidence: 99%

Molecular Physiology of P2X Receptors

North

2002

Physiological Reviews

2,674

128

3,397

View full text Add to dashboard Cite

P2X receptors are membrane ion channels that open in response to the binding of extracellular ATP. Seven genes in vertebrates encode P2X receptor subunits, which are 40–50% identical in amino acid sequence. Each subunit has two transmembrane domains, separated by an extracellular domain (∼280 amino acids). Channels form as multimers of several subunits. Homomeric P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 channels and heteromeric P2X2/3 and P2X1/5 channels have been most fully characterized following heterologous expression. Some agonists (e.g., αβ-methylene ATP) and antagonists [e.g., 2′,3′- O-(2,4,6-trinitrophenyl)-ATP] are strongly selective for receptors containing P2X1 and P2X3subunits. All P2X receptors are permeable to small monovalent cations; some have significant calcium or anion permeability. In many cells, activation of homomeric P2X7 receptors induces a permeability increase to larger organic cations including some fluorescent dyes and also signals to the cytoskeleton; these changes probably involve additional interacting proteins. P2X receptors are abundantly distributed, and functional responses are seen in neurons, glia, epithelia, endothelia, bone, muscle, and hemopoietic tissues. The molecular composition of native receptors is becoming understood, and some cells express more than one type of P2X receptor. On smooth muscles, P2X receptors respond to ATP released from sympathetic motor nerves (e.g., in ejaculation). On sensory nerves, they are involved in the initiation of afferent signals in several viscera (e.g., bladder, intestine) and play a key role in sensing tissue-damaging and inflammatory stimuli. Paracrine roles for ATP signaling through P2X receptors are likely in neurohypophysis, ducted glands, airway epithelia, kidney, bone, and hemopoietic tissues. In the last case, P2X7 receptor activation stimulates cytokine release by engaging intracellular signaling pathways.

show abstract

“…Whether NE and ATP are released from the same site or from different varicosities (Driessen et al, 1993;Westfall et al, 1996;Bobalova and Mutafova-Yambolieva, 2001;Stjarne, 2001;Brock and Tan, 2004), ATP is likely to modulate NE release in either case (von Kugelgen et al, 1999;Sperlágh et al, 2000;Sesti et al, 2002). Indeed, once released, neurotransmitter ATP promotes NE release by activating presynaptic P2X purinoceptors (P2XRs) (Boehm, 1999;Sperlágh et al, 2000;Sesti et al, 2002;Queiroz et al, 2003).…”

mentioning

confidence: 99%

Ectonucleoside Triphosphate Diphosphohydrolase1/CD39, Localized in Neurons of Human and Porcine Heart, Modulates ATP-Induced Norepinephrine Exocytosis

Machida¹,

Heerdt²,

Reid³

et al. 2005

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Using a guinea pig heart synaptosomal preparation, we previously observed that norepinephrine (NE) exocytosis was attenuated by a blockade of P2X purinoceptors, potentiated by inhibition of ectonucleoside triphosphate diphosphohydrolase-1 (E-NTPDase1)/CD39, and reduced by soluble CD39, a recombinant form of human E-NTPDase1/CD39. This suggests that norepinephrine and ATP are coreleased upon depolarization of cardiac sympathetic nerve endings and that ATP enhances norepinephrine exocytosis by an action modulated by E-NTPDase1/CD39 activity. Whether E-NTPDase1/CD39 is localized to cardiac neurons and modulates norepinephrine exocytosis in intact heart tissue remained untested. We report that E-NTPDase1/CD39 is selectively localized in human and porcine cardiac neurons and that depolarization of porcine heart tissue elicits -conotoxin-inhibitable release of both norepinephrine and ATP. Inhibition of E-NTPDase1/CD39 with ARL67156 markedly potentiated ATP release, demonstrating that E-NTPDase1/CD39 is a major determinant of ATP availability at sympathetic nerve terminals. Notably, inhibition of E-NTPDase1/CD39 enhanced both ATP and NE exocytosis, whereas administration of soluble CD39 reduced both ATP and NE exocytosis. The strong correlation between ATP and norepinephrine release was abolished in the presence of the purinergic P2X receptor (P2XR) antagonist pyridoxal-phosphate-6-azophenyl-2Ј,4Ј-disulfonic acid (PPADS). We conclude that released ATP governs norepinephrine exocytosis by activating presynaptic P2XR and that this action is controlled by neuronal E-NTPDase1/CD39. Clinically, excessive norepinephrine release is a major cause of arrhythmic and coronary vascular dysfunction during myocardial ischemia. By curtailing NE release, in addition to its effects as an antithrombotic agent, soluble CD39 may constitute a novel therapeutic approach to ischemic complications in the myocardium.It is now well established that norepinephrine (NE) and ATP function as cotransmitters at peripheral adrenergic neuroeffector junctions (Burnstock, 1999;Sneddon et al., 1999). Whether NE and ATP are released from the same site or from different varicosities (Driessen et al

show abstract

Role of action potentials and calcium influx in ATP- and UDP-induced noradrenaline release from rat cultured sympathetic neurones

Cited by 31 publications

References 3 publications

P2Y-Receptors Mediating an Inhibition of the Evoked Entry of Calcium through N-Type Calcium Channels at Neuronal Processes

P2Y-Receptors Mediating an Inhibition of the Evoked Entry of Calcium through N-Type Calcium Channels at Neuronal Processes

Molecular Physiology of P2X Receptors

Ectonucleoside Triphosphate Diphosphohydrolase1/CD39, Localized in Neurons of Human and Porcine Heart, Modulates ATP-Induced Norepinephrine Exocytosis

Contact Info

Product

Resources

About