Role of calcium channels in parathyroid hormone secretion.
Experimental evidence exists for the presence of parathyroid cell membrane calcium channels that respond to plasma calcium. In previous reports, the effects of various calcium channel agents on PTH secretion have revealed conflicting results. To resolve some of these inconsistencies, we have compared the pure calcium channel agonist, (+)202-791, and its antagonistic enantiomer (-)202-791 with other calcium channel agents--verapamil, nifedipine, and (+)Bay-K-8644. The agonist (+)202-791 enhanced 45Ca+2 uptake and decreased PTH secretion, while the antagonist (-)202-791 decreased 45Ca+2 uptake and increased PTH secretion. The calcium channel appears coupled to a G-protein as indicated by pertussis toxin treatment of the cells. The enantiomers (+/-)202-791 had little effect on intracellular cAMP production suggesting that the calcium channel may not be responsible for the previously observed calcium-mediated changes in cAMP. The antagonist (-)202-791 increased the phosphorylation of a 60-kd protein. The enantiomers (+/-)202-791 did not alter the effect of depolarizing concentrations of potassium on PTH secretion. Our results suggest that calcium channels provide a pathway for the movement of calcium across the plasma membrane and that this pool of calcium regulates, at least in part, PTH secretion.
Pocotte
S L
SL
Laboratory of Biophysics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Ehrenstein
G
G
Fitzpatrick
L A
LA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015759:Ionomycin / Q000494:pharmacology; D007553:Isotope Labeling; D009539:Nicotinic Acids / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010069:Oxadiazoles; D010280:Parathyroid Glands / Q000166:cytology / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D037342:Pertussis Toxin; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D011863:Radioimmunoassay; D013237:Stereoisomerism; D014700:Verapamil / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009539:Nicotinic Acids; D010069:Oxadiazoles; D010281:Parathyroid Hormone; D010566:Virulence Factors, Bordetella; C049834:PN 202-791; D015759:Ionomycin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D000242:Cyclic AMP; D037342:Pertussis Toxin; D009543:Nifedipine; D011188:Potassium