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Post- and prejunctional consequences of ecto-ATPase inhibition: electrical and contractile studies in guinea-pig vas deferens

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Title Post- and prejunctional consequences of ecto-ATPase inhibition: electrical and contractile studies in guinea-pig vas deferens
 
Creator GHILDYAL, P
PALANI, D
MANCHANDA, R
 
Subject excitatory junction potentials
sympathetic purinergic neurotransmission
receptor-mediated enhancement
central-nervous-system
smooth-muscle cells
dorsal-horn neurons
adenosine-triphosphate
synaptic potentials
neuromuscular-transmission
transmitter release
 
Description At sites of purinergic neurotransmission, synaptic ecto-ATPase is believed to limit the actions of ATP following its neural release. However, details of the modulation by this enzyme of the ATP-mediated conductance change and the possible mechanisms mediating this modulation remain unelucidated. We have addressed these issues by studying the effect of ARL 67156, a selective ecto-ATPase inhibitor, on ATP-mediated electrical and contractile activity in the sympathetically innervated guinea-pig vas deferens. ARL 67156 at 100 mu m significantly potentiated the amplitude of spontaneous excitatory junction potentials (SEJPs) by 81.1% (P < 0.01) and prolonged their time courses (rise time by 49.7%, decay time constant by 38.2%; P < 0.01). Moreover, the frequency of occurrence of SEJPs was strikingly increased (from 0.28 +/- 0.13 to 0.90 +/- 0.26 Hz; P < 0.01), indicating an additional, primarily presynaptic, effect of ecto-ATPase inhibition. The frequency of occurrence of discrete events (DEs), which represent nerve stimulation-evoked quantal release of neurotransmitter, was also increased (similar to 6-fold; P < 0.01), along with the appearance of DEs at previously 'silent' latencies. Purinergic contractions of the vas deferens were potentiated significantly (P < 0.01) by ARL 67156; these potentiated contractions were suppressed by the A1 agonist adenosine (P < 0.01) but left unaffected by the A1 antagonist 8-phenyltheophylline (8-PT). Our results indicate (i) that ecto-ATPase activity, in addition to modulating the ATP-mediated postjunctional conductance change, may regulate transmitter release prejunctionally under physiological conditions, and (ii) that the prejunctional regulation may be mediated primarily via presynaptic P2X, rather than A1, receptors.
 
Publisher BLACKWELL PUBLISHING
 
Date 2011-07-19T04:27:01Z
2011-12-26T12:51:00Z
2011-12-27T05:37:16Z
2011-07-19T04:27:01Z
2011-12-26T12:51:00Z
2011-12-27T05:37:16Z
2006
 
Type Article
 
Identifier JOURNAL OF PHYSIOLOGY-LONDON, 575(2), 469-480
0022-3751
http://dx.doi.org/10.1113/jphysiol.2006.109678
http://dspace.library.iitb.ac.in/xmlui/handle/10054/5172
http://hdl.handle.net/10054/5172
 
Language en