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.
- Research Organization:
- Univ. of Texas Health Science Center, San Antonio (USA)
- OSTI ID:
- 6569423
- Journal Information:
- Endocrinology; (United States), Vol. 124:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
PARATHORMONE
SECRETION
TOXINS
BIOLOGICAL EFFECTS
CALCIUM
CALCIUM ISOTOPES
CATTLE
DOSE-RESPONSE RELATIONSHIPS
EGTA
INHIBITION
PARATHYROID GLANDS
ALCOHOLS
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METALS
ANIMALS
ANTIGENS
BODY
CARBOXYLIC ACIDS
CHELATING AGENTS
DOMESTIC ANIMALS
ELEMENTS
ENDOCRINE GLANDS
GLANDS
GLYCOLS
HORMONES
HYDROXY COMPOUNDS
ISOTOPES
MAMMALS
MATERIALS
METALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
RUMINANTS
TOXIC MATERIALS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques