Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator.
Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release.
Fitzpatrick
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LA
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7877.
Yasumoto
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T
Aurbach
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D000818:Animals; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000502:physiology*; D002132:Calcium Radioisotopes / Q000378:metabolism; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D008387:Marine Toxins / Q000494:pharmacology*; D009539:Nicotinic Acids / Q000494:pharmacology; D010069:Oxadiazoles; D035964:Oxocins; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000095702:Polyether Toxins
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D004533:Egtazic Acid; D008387:Marine Toxins; D009539:Nicotinic Acids; D010069:Oxadiazoles; D035964:Oxocins; D010281:Parathyroid Hormone; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella; C049834:PN 202-791; C020394:maitotoxin; D000095702:Polyether Toxins