Characterization of palytoxin-induced catecholamine secretion from cultured bovine adrenal chromaffin cells. Effects of Na(+)- and Ca(2+)-channel blockers.
The effect of palytoxin (PTX), a potent marine toxin, on catecholamine (CA) secretion from cultured bovine adrenal chromaffin cells was examined. PTX at concentrations of over 10(-10) M induced CA secretion concentration-dependently. About 40-50% of the total cellular CA was secreted during 20-min incubation with 3 x 10(-8) M PTX. PTX-induced CA secretion was dependent on both extracellular Na+ and Ca2+. PTX caused increases in [22Na](+)- and [45Ca](2+)-influxes into the cells. Increase in [22Na](+)-influx was observed at concentrations of over 10(-11) M PTX and was maximal at 10(-10) M PTX and then gradually decreased at higher concentrations that induced [45Ca](2+)-influx and CA secretion. On the other hand, increase in [45Ca](2+)-influx was observed at concentrations of over 10(-10) M PTX and increased with increase in concentration of PTX. This concentration-response curve for PTX-induced [45Ca](2+)-influx was similar to that for PTX-induced CA secretion. The CA secretion and [22Na](+)- and [45Ca](2+)-influxes induced by PTX were not affected by tetrodotoxin (TTX), but were significantly inhibited by quinidine and aprindine(mexiletine), antiarrythmic drugs known to block Na(+)-channels. Ca(2+)-channel blockers such as nifedipine, verapamil, Co2+, Cd2+, inhibited both CA secretion and [45Ca](2+)-influx induced by PTX. These results indicate that PTX-induced CA secretion is mediated by activation of Na(+)-dependent, TTX-insensitive voltage-dependent Ca(2+)-channels, and is inhibited by quinidine and aprindine through their inhibitory effects on the Na(+)- and Ca(2+)-influxes into the cells induced by PTX.
Department of Cardiovascular Surgery, Tokushima University School of Medicine, Japan.
M
M
Yoshizumi
A
A
Nakanishi
H
H
Houchi
K
K
Morita
I
I
Katoh
M
M
Oka
D000178:Acrylamides; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000378:metabolism / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects; D002838:Chromaffin System / Q000187:drug effects* / Q000378:metabolism; D003064:Cnidarian Venoms / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015222:Sodium Channels / Q000187:drug effects*; D012965:Sodium Chloride / Q000378:metabolism / Q000494:pharmacology; D012979:Sodium Radioisotopes; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D000095702:Polyether Toxins
D000178:Acrylamides; D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D002122:Calcium Chloride; D002132:Calcium Radioisotopes; D002395:Catecholamines; D003064:Cnidarian Venoms; D015222:Sodium Channels; D012965:Sodium Chloride; D012979:Sodium Radioisotopes; D013779:Tetrodotoxin; D014701:Veratridine; C010272:palytoxin; D000095702:Polyether Toxins