Omega-conotoxin differentially blocks acetylcholine and adenosine triphosphate releases from Torpedo synaptosomes.
We have examined the effect of several blockers of voltage-sensitive calcium channels on the release of acetylcholine and ATP from synaptosomes isolated from Torpedo marmorata electric organ. Depolarization of these nerve terminals with high K(+)-containing solutions resulted in a calcium-dependent release of both molecules. Cadmium ions (10(-6) to 10(-3) M) inhibited similarly both releases whereas nickel ions (10(-4) M) in the external medium did not affect either neurotransmitter or nucleotide release. Both releases were completely resistant to the effect of 1,4-dihydropyridines (antagonists nimodipine, nifedipine and agonist Bay K 8644) and of a related compound (diltiazem) at concentrations up to 10(-5) M. These drugs failed to cause any effect even when synaptosomes were submaximally depolarized during incubation. Omega-conotoxin (10(-8) to 5 x 10(-5) M) showed a differential effect on acetylcholine and ATP releases. Nucleotide release was inhibited 90% at the highest concentration tested (50 microns) while acetylcholine release was only moderately decreased (30%). EC50 values for acetylcholine and ATP were of 167 and 2 microM respectively. The results suggest the implication of different types of calcium channels in the release of these molecules.
Fariñas
I
I
Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Hospital de Bellvitge, Universitat de Bärcelona, Spain.
Solsona
C
C
Marsal
J
J
D000109:Acetylcholine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology; D004557:Electric Organ / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D010456:Peptides, Cyclic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014101:Torpedo / Q000378:metabolism*; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; D000001:Calcimycin; D000255:Adenosine Triphosphate; D000109:Acetylcholine; D002118:Calcium