omega-Agatoxin IVA blocks nicotinic receptor channels in bovine chromaffin cells.
We have studied the contribution of P-type voltage-dependent Ca2+ channels to both catacholamine (CA) and ATP secretion from bovine chromaffin cells induced by high K+ or nicotine using omega-agatoxin IVA, a selective blocker of P-type voltage-dependent Ca2+ channels. We found that high K+ (75 mM) induced the release of about 13% of norepinephrine, 5% epinephrine and 11% ATP, and that omega-agatoxin (100 nM) did not affect this secretion. However, both nicotine-induced CA and ATP secretion were significantly blocked (about 50%) by omega-agatoxin IVA (100 nM). In addition, this toxin also reversibly blocked (about 70%) the inward current induced by nicotine in bovine chromaffin cells. The results suggest that, besides its known action of blocking P-type voltage-dependent channels, omega-agatoxin is a potent and reversible blocker of the nicotinic receptor channel in chromaffin cells, and that this action would explain the blockade of nicotine-induced secretion.
Granja
R
R
Departamento de Farmacología, Universidad de Alicante, Spain.
Fernández-Fernández
J M
JM
Izaguirre
V
V
González-García
C
C
Ceña
V
V
D000255:Adenosine Triphosphate / Q000378:metabolism; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004837:Epinephrine / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology*; D020867:omega-Agatoxin IVA
D015220:Calcium Channels; D011978:Receptors, Nicotinic; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D009538:Nicotine; D000255:Adenosine Triphosphate; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine