On the role of calcium ions in the presynaptic alpha-receptor mediated inhibition of [3H]noradrenaline release from rat brain cortex synaptosomes.
Rat brain cortex synaptosomes, previously labeled by incubation with [3H]noradrenaline ([3H]NA) were continuously superfused with Krebs-Ringer media. Release of [3H]NA was induced by superfusion with medium containing either 15 mM K+, 20 microM veratrine or 1 microM of the calcium-ionophore A 23187 and was strongly dependent on the concentration of Ca2+ in the medium. Noradrenaline (1 microM, in the presence of the uptake inhibitor desipramine) inhibited K+-induced [3H]NA release by activation of presynaptic alpha-receptors. When the Ca2+-concentration in the medium was reduced, or the Mg2+-concentration increased, [3H]NA release appeared to be more susceptible to alpha-receptor mediated inhibition. Noradrenaline (1 microM) inhibited [3H]NA release induced by 15 mM K+, in the presence of 0.075 Ca2+ and 10 mM Mg2+, by 86%. Veratrine-induced release was also inhibited by alpha-receptor activation. However, [3H]NA release induced by the calcium-ionophore was not affected by alpha-receptor agonists. These results strongly support the view that alpha-receptor activation results in a decrease of the availability of Ca2+ for stimulus-secretion coupling processes. Presumably this is effected by an inhibition of voltage-sensitive calcium channels in the neuronal membrane associated with neurotransmitter release.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects*; D014702:Veratrine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D000001:Calcimycin; D014702:Veratrine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine