Ecto-Nucleotidases in Isolated Intact Rat Vagi, Nodose Ganglia, and Superior Cervical Ganglia

Connolly, G.P.; Demaine, C.; Duley, JA

doi:10.1007/978-1-4615-5381-6_147

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…In the case of NTPDase8, ARL 67156 would be expected to slow down nucleotide hydrolysis in mouse, but not in human, tissues. Therefore, in tissues where ARL 67156 was described to block ATP hydrolysis such as vas deferens, superior cervical ganglia, chromaffin cell, urinary bladder, ear and tail arteries, and parotid acinar cells (Crack et al , 1995; Khakh et al , 1995; Westfall et al , 1996, 1997a, 2000b; Connolly et al , 1998; McLaren et al , 1998; Dowd et al , 1999; Drakulich et al , 2004; Ghildyal and Manchanda, 2004), NTPDase1, NTPDase3 and/or NPP1 would be expected to play a pivotal role in extracellular nucleotide hydrolysis. Indeed the inhibition of ATP hydrolysis in ear and tail arteries by ARL 67156 could be explained by NTPDase1 as it is the major ectonucleotidase expressed by the vascular endothelium (Kaczmarek et al , 1996; Marcus et al , 1997; Enjyoji et al , 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed the inhibition of ATP hydrolysis in ear and tail arteries by ARL 67156 could be explained by NTPDase1 as it is the major ectonucleotidase expressed by the vascular endothelium (Kaczmarek et al , 1996; Marcus et al , 1997; Enjyoji et al , 1999). In other tissues with high ectonucleotidase activities and where ARL 67156 had no effect, NTPDase2, NPP3, or potentially NTPDase8 depending of the species, would be expected to be more important as for example in heart and nodose ganglia (Connolly et al , 1998; Erga et al , 2000). Hence, the lack of inhibition by ARL 67156 of the activity from guinea‐pig hearts (Erga et al , 2000) could be explained by NTPDase2 that is highly expressed in this tissue (Kegel et al , 1997; Sévigny et al , 2002).…”

Section: Discussionmentioning

confidence: 99%

“…(1995) as a selective inhibitor of ecto‐ATPase activity from blood cells. Since this original report, ARL 67156 was shown to inhibit ecto‐ATPase activity in various tissues from different species: smooth muscle membranes of mouse, rat, rabbit and guinea‐pig vas deferens (Khakh et al , 1995; Westfall et al , 2000b; Ghildyal and Manchanda, 2004), rat superior cervical ganglia (Connolly et al , 1998), bovine chromaffin cells (Drakulich et al , 2004) and rat parotid acinar cells (Dowd et al , 1999). However, it did not block ATPase activity from guinea‐pig hearts (Erga et al , 2000) nor from rat nodose ganglia (Connolly et al , 1998).…”

Section: Introductionmentioning

confidence: 99%

“…Since this original report, ARL 67156 was shown to inhibit ecto‐ATPase activity in various tissues from different species: smooth muscle membranes of mouse, rat, rabbit and guinea‐pig vas deferens (Khakh et al , 1995; Westfall et al , 2000b; Ghildyal and Manchanda, 2004), rat superior cervical ganglia (Connolly et al , 1998), bovine chromaffin cells (Drakulich et al , 2004) and rat parotid acinar cells (Dowd et al , 1999). However, it did not block ATPase activity from guinea‐pig hearts (Erga et al , 2000) nor from rat nodose ganglia (Connolly et al , 1998). In agreement with the inhibition of ATP hydrolysis, ARL 67156 was shown to potentiate the contraction evoked by exogenous ATP in guinea‐pig isolated vas deferens, in urinary bladder (Westfall et al , 1996, 1997a) and in rabbit ear artery (Crack et al , 1995) as well as the responses to endogenously released ATP induced by noradrenaline, KCl, acetylcholine or histamine (Westfall et al , 1996, 1997a).…”

Section: Introductionmentioning

confidence: 99%

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Specificity of the ecto‐ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases

Lévesque

Lavoie

Lecka

et al. 2007

British J Pharmacology

184

178

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Background and purpose: ARL 67156, 6-N,N-Diethyl-D-b-g-dibromomethylene adenosine triphosphate, originally named FPL 67156, is the only commercially available inhibitor of ecto-ATPases. Since the first report on this molecule, various ectonucleotidases responsible for the hydrolysis of ATP at the cell surface have been cloned and characterized. In this work, we identified the ectonucleotidases inhibited by ARL 67156. Experimental approach: The effect of ARL 67156 on recombinant NTPDase1, 2, 3 & 8 (mouse and human), NPP1, NPP3 and ecto-5 0 -nucleotidase (human) have been evaluated. The inhibition of the activity of NTPDases (using the following substrates: ATP, ADP, UTP), NPPs (pnp-TMP, Ap 3 A) and ecto-5 0 -nucleotidase (AMP) was measured by colorimetric or HPLC assays. Key results: ARL 67156 was a weak competitive inhibitor of human NTPDase1, NTPDase3 and NPP1 with K i of 1173, 1874 and 1273 mM, respectively. At concentrations used in the literature (50-100 mM), ARL 67156 partially but significantly inhibited the mouse and human forms of these enzymes. NTPDase2, NTPDase8, NPP3 and ecto-5 0 -nucleotidase activities were less affected. Importantly, ARL 67156 was not hydrolysed by either human NTPDase1, 2, 3, 8, NPP1 or NPP3. Conclusions and implications:In cell environments where NTPDase1, NTPDase3, NPP1 or mouse NTPDase8 are present, ARL 67156 would prolong the effect of endogenously released ATP on P2 receptors. However, it does not block any ectonucleotidases efficiently when high concentrations of substrates are present, such as in biochemical, pharmacological or P2X 7 assays. In addition, ARL 67156 is not an effective inhibitor of NTPDase2, human NTPDase8, NPP3 and ecto-5 0 -nucleotidase.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Specificity of the ecto‐ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases

Lévesque

Lavoie

Lecka

et al. 2007

British J Pharmacology

184

178

View full text Add to dashboard Cite

show abstract

“…This implies that ATPase is present in the tongue leading to a rapid degradation of ATP. Indeed, ATPase has been shown to be present in many tissues (Knowles et al 1983; Connolly et al 1998). The combination of receptor desensitisation and rapid degradation of ATP by ATPase will have major influences on the efficacy of ATP analogues when applied onto tissue blocks in, for example, isolated intact sensory ganglia (e.g.…”

Section: Discussionmentioning

confidence: 99%

P2X purinoceptor‐mediated excitation of trigeminal lingual nerve terminals in an in vitro intra‐arterially perfused rat tongue preparation

Rong

Burnstock

Spyer

2000

The Journal of Physiology

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A novel in vitro intra‐arterially perfused adult rat tongue‐nerve preparation was used to explore the possible actions of P2X purinoceptor agonists (ATP and α,β‐methylene ATP (α,β‐meATP)) on sensory nerve terminals innervating the rat tongue. We made whole‐nerve recordings of the trigeminal branch of the lingual nerve (LN), which conducts general sensory information (pain, temperature, touch, etc.), and the chorda tympani (CT), which conducts taste information. Changes in LN and CT activity following intra‐arterial application of P2X agonists were compared. In seven preparations, bolus close‐arterial injection of ATP (30–3000 μM, 0.1 ml) or α,β‐meATP (10–300 μM, 0.1 ml) induced a rapid (< 1 s after injection), dose‐related increase in LN activity that decayed within a few seconds. The minimal concentration of ATP (100 μM) required to elicit a response was about 10‐fold higher than that of α,β‐meATP (10 μM). Bolus injection of ATP or α,β‐meATP induced a moderate decrease in firing frequency in three of seven CT preparations. LN responses to P2X agonists showed signs of rapid desensitisation with the peak frequency of discharge being smaller when the agonists were applied at short intervals. Suramin (200 μM) or PPADS (200 μM) applied by intra‐arterial perfusion each antagonised the rapid increase in LN activity following application of α,β‐meATP (100 μM). Capsaicin (10 μM, 0.1 ml, n= 5 preparations) was injected intra‐arterially to desensitise nociceptive fibres. This was found to block (n= 2) or greatly reduce (n= 3) the excitatory effects of α,β‐meATP (100 μM, 0.1 ml) on LN activity, implying that only capsaicin‐sensitive nociceptive fibres in LN were responsive to P2X agonists. In contrast to the consistent excitatory responses in LN activity following fast application of P2X agonists as bolus, a variable and moderate change in discharge rate of LN and no change in CT activity (n= 5) was observed after applying ATP (100–300 μM, n= 21) or α,β‐meATP (100–300 μM, n= 14) by intra‐arterial perfusion. The variable responses in LN activity to slow perfusion in contrast to close‐arterial bolus injection are consistent with activation of the rapidly desensitising P2X3 receptors. In summary, ATP and α,β‐meATP preferentially activate general sensory afferent fibres (LN) but not taste fibres (CT). We suggest that the increase in whole‐nerve activity of LN following application of P2X agonists represents activation of nociceptive fibres which possess P2X3 receptors. Our data indicate that ATP and P2X3 receptors may play a role in nociception, rather than taste sensation in the tongue.

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Uridine and Pyrimidine Nucleotides in Cell Function

Connolly¹

2001

Purinergic and Pyrimidinergic Signalling I

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Ecto-Nucleotidases in Isolated Intact Rat Vagi, Nodose Ganglia, and Superior Cervical Ganglia

Cited by 8 publications

References 10 publications

Specificity of the ecto‐ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases

Specificity of the ecto‐ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases

P2X purinoceptor‐mediated excitation of trigeminal lingual nerve terminals in an in vitro intra‐arterially perfused rat tongue preparation

Uridine and Pyrimidine Nucleotides in Cell Function

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