A2A adenosine receptor facilitation of neuromuscular transmission:: Influence of stimulus paradigm on calcium mobilization

被引:28
作者
Correia-de-Sá, P
Timóteo, MA
Ribeiro, JA
机构
[1] Univ Porto, Inst Ciencias biomed Abel Salazar, Farmacol Lab, P-4099003 Porto, Portugal
[2] Univ Lisbon, Fac Med, Neurosci Lab, P-1699 Lisbon, Portugal
关键词
A(2A) adenosine receptor; calcium channel blockers; thapsigargin; stimulation parameters; H-3]acetylcholine release; neuromuscular junction;
D O I
10.1046/j.1471-4159.2000.0742462.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The influence of stimulus pulse duration on calcium mobilization triggering facilitation of evoked [H-3]acetylcholine ([H-3]ACh) release by the A(2A) adenosine receptor agonist CGS 21680C was studied in the rat phrenic nerve-hemidiaphragm. The P-type calcium channel blocker omega-agatoxin IVA (100 nM) decreased [H-3]ACh release evoked with pulses of 0.04-ms duration, whereas nifedipine (1 mu M) inhibited transmitter release with pulses of 1-ms duration. Depletion of intracellular calcium stores by thapsigargin (2 mu M) decreased H-3]ACh release evoked by pulses of 1 ms, an effect observed even in the absence of extracellular calcium. With short (0.04-ms) stimulation pulses, when P-type calcium influx triggered transmitter release, facilitation of H-3]ACh release by CGS 21680C (3 nM) was attenuated by both thapsigargin (2 mu M) and nifedipine (1 mu M). With longer stimuli (1 ms), a situation in which both thapsigargin-sensitive internal stores and L-type channels are involved in ACh release, pretreatment with either omega-agatoxin IVA (100 nM) or nifedipine (1 mu M) reduced the facilitatory effect of CGS 21680C (3 nM). The results suggest that A(2A) receptor activation facilitates ACh release from motor nerve endings through alternatively mobilizing the available calcium pools (thapsigargin-sensitive internal stores and/or P- or L-type channels) that are not committed to the release process in each stimulation condition.
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页码:2462 / 2469
页数:8
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