Effects of botulinum A toxin on presynaptic modulation of evoked transmitter release.
A possible influence of botulinum A toxin on the modulation of evoked neurotransmitter release was investigated in hippocampus tissue. Rabbit hippocampal slices prelabelled with [3H]noradrenaline ([3H]NA), [3H]5-hydroxytryptamine ([3H]5-HT) or [3H]choline were superfused with physiological medium and were stimulated electrically during superfusion. The evoked release of [3H]NA, [3H]5-HT and [3H]acetylcholine [( 3H]ACh) was inhibited by botulinum A toxin in a concentration- and time-dependent manner. Neither the inhibition of release of [3H]NA and [3H]5-HT by the alpha 2-adrenoceptor agonist clonidine nor facilitation of release in the presence of alpha 2-antagonists were influenced by pretreatment of the tissue with botulinum toxin. The toxin caused no [32P]ADP ribosylation of synaptosomal proteins of hippocampus. The facilitation of the stimulation-induced [3H]NA and [3H]5-HT release by the specific protein kinase C (PKC) activator 4 beta-phorbol-12,13-dibutyrate (PDB) was significantly diminished by botulinum A toxin. These results show that the evoked transmitter release is inhibited by botulinum A toxin by a mechanism which does not involve ADP ribosylation or an interaction with the alpha 2-adrenoceptor mechanism.
Nakov
R
R
Institute for Pharmacology and Pharmacy, Medical Academy, Sofia, Bulgaria.
Habermann
E
E
Hertting
G
G
Wurster
S
S
Allgaier
C
C
D000109:Acetylcholine / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D018377:Neurotransmitter Agents; D015016:Yohimbine; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D000244:Adenosine Diphosphate; D001905:Botulinum Toxins; D003000:Clonidine; D000109:Acetylcholine; D009638:Norepinephrine