Role of external and internal calcium on heterocarrier-mediated transmitter release.
Release-regulating heterocarriers exist on brain nerve endings. We have investigated in this study the mechanisms involved in the neurotransmitter release evoked by GABA heterocarrier activation. GABA increased the basal release of [3H]acetylcholine and [3H]noradrenaline from rat hippocampal synaptosomes and of [3H]dopamine from striatal synaptosomes. These GABA effects, insensitive to GABA receptor antagonists, were prevented by inhibiting GABA uptake but not by blocking noradrenaline, choline, or dopamine transport. Lack of extracellular Ca2+ or addition of tetrodotoxin selectively abolished the GABA-evoked release of [3H]noradrenaline, leaving unaffected that of [3H]acetylcholine or [3H]dopamine. 1,2-Bis(2-aminophenoxyl)-ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) or vesamicol attenuated the release of [3H]acetylcholine elicited by GABA. Reserpine, but not BAPTA-AM, prevented the effect of GABA on [3H] dopamine release. Autoreceptor activation inhibited the GABA-evoked release of [3H]noradrenaline but not that of [3H]acetylcholine or [3H]dopamine. It is concluded that (a) the release of [3H]noradrenaline consequent to activation of GABA heterocarriers sited on noradrenergic terminals meets the criteria of a conventional exocytotic process, (b) the extracellular [Ca2+]-independent releases of [3H]acetylcholine and [3H]dopamine appear to occur from vesicles possibly through involvement of intraterminal Ca2+, and (c) autoreceptor activation only affects heterocarrier-mediated vesicular release linked to entry of extracellular Ca2+.
Fassio
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Istituto di Farmacologia e Farmacognosia, Università di Genova, Italy.
Bonanno
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Fontana
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Usai
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Marchi
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D000109:Acetylcholine / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology* / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002614:Chelating Agents; D002794:Choline / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives; D004873:Ergolines / Q000494:pharmacology; D018757:GABA Modulators / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010095:Oxotremorine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure; D014316:Tritium / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002352:Carrier Proteins; D002614:Chelating Agents; D018491:Dopamine Agonists; D004873:Ergolines; D018757:GABA Modulators; D018721:Muscarinic Agonists; D009467:Neuromuscular Depolarizing Agents; D018377:Neurotransmitter Agents; D010880:Piperidines; D014316:Tritium; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D019257:Quinpirole; D015016:Yohimbine; C006189:vesamicol; D004533:Egtazic Acid; D010095:Oxotremorine; D003000:Clonidine; D002794:Choline; D000109:Acetylcholine; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine