Contribution of intra- and extracellular Ca2+ to noradrenaline exocytosis induced by ouabain and monensin from guinea-pig vas deferens.
1. Contributions of intra- and extracellular Ca2+ to noradrenaline (NA) release evoked by increasing intracellular Na+ concentrations (ouabain plus monensin) from adrenergic nerves of guinea-pig vas deferens were evaluated under conditions eliminating carrier-mediated NA release (with 100 microM cocaine). 2. Ouabain (100 microM) plus monensin (10 microM), unlike 100 mM KCl, produced a marked NA release which was unchanged by Ca(2+)-removal. 3. In normal solution but not in Ca(2+)-free solution, the release of NA evoked by ouabain plus monensin was reduced by adenosine, clonidine and neuropeptide Y, and by Ca(2+)-channel blockers such as omega-conotoxin GVIA and nifedipine. The release of NA was also decreased by cromakalim in a glibenclamide-sensitive fashion. 4. In contrast, in the absence but not in the presence of Ca2+, the drug-evoked NA release was inhibited by mitochondrial inhibitors (carbonylcyanide-m-chlorophenylhydrazone and oligomycin) and further by immobilizers of intracellular Ca2+ (TMB-8 and BAPTA-AM) and calmodulin antagonists (W-7 and trifluoperazine). 5. These findings suggest that the release of NA evoked by elevation of [Na+]i from adrenergic nerves in the presence and absence of Ca2+ involves, in part, exocytotic processes which are triggered by depolarization-induced Ca2+ influx and by utilization of Ca2+ from intracellular Ca2+ store sites such as mitochondria, respectively.
Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
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Katsuragi
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Ogawa
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Furukawa
D000818:Animals; D002118:Calcium / Q000502:physiology*; D005089:Exocytosis; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008985:Monensin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase; D014649:Vas Deferens / Q000378:metabolism*
D010042:Ouabain; D011189:Potassium Chloride; D008985:Monensin; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D009638:Norepinephrine