A(2A) adenosine receptor facilitation of neuromuscular transmission: influence of stimulus paradigm on calcium mobilization.
The influence of stimulus pulse duration on calcium mobilization triggering facilitation of evoked [(3)H]acetylcholine ([(3)H]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 [(3)H]ACh release evoked with pulses of 0.04-ms duration, whereas nifedipine (1 microM) inhibited transmitter release with pulses of 1-ms duration. Depletion of intracellular calcium stores by thapsigargin (2 microM) decreased [(3)H]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 [(3)H]ACh release by CGS 21680C (3 nM) was attenuated by both thapsigargin (2 microM) and nifedipine (1 microM). 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 microM) 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.
Correia-de-Sá
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Laboratory of Pharmacology, Instituto de Ciências Biomédicas de Abel Salazar, University of Oporto, Porto, Portugal.
Timóteo
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Ribeiro
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D000109:Acetylcholine / Q000493:pharmacokinetics; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D019256:Cadmium Chloride / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D020865:Calcium Channels, P-Type / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009046:Motor Neurons / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D009469:Neuromuscular Junction / Q000737:chemistry / Q000201:enzymology*; D010627:Phenethylamines / Q000494:pharmacology; D010791:Phrenic Nerve / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology; D014316:Tritium; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020865:Calcium Channels, P-Type; D004791:Enzyme Inhibitors; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; D014316:Tritium; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C075851:omega-conotoxin-MVIIC; D019284:Thapsigargin; D020866:omega-Conotoxin GVIA; D000252:Calcium-Transporting ATPases; D019256:Cadmium Chloride; D000241:Adenosine; D000109:Acetylcholine; D002118:Calcium