title: Inhibition of parathyroid hormone secretion by caffeine in human parathyroid cells.
abstract: OBJECTIVE
  Caffeine is a highly consumed psychoactive substance present in our daily drinks. Independent studies have reported associations between caffeine consumption, low bone mineral density, and urinary calcium loss, as well as impaired bone development in vitro and in vivo. Calcium (Ca(2+)), vitamin D, and PTH are critical regulators of bone remodeling. A possible association between caffeine and parathyroid gland function has been suggested in the literature.
  
  
  METHODS
  Effects of caffeine on PTH secretion and Ca(2+) levels were determined by batch incubation and Fura-2, respectively, in pathological parathyroid cells. Protein expressions were studied by Western blot and immunohistochemistry in normal and parathyroid adenoma tissues. Alterations in gene expressions of adenosine receptor A1 (ADORA1) and A2 (ADORA2A) and PTH were quantified by PCR; intracellular cAMP levels and protein kinase A activity were analyzed by an antibody-based assay.
  
  
  RESULTS
  We studied physiological concentrations of caffeine ranging from 1 to 50 μm and found that 50 μm caffeine caused a significant decrease of PTH secretion and PTH gene expression. This decrease occurred in parallel with a decrease of the intracellular cAMP level, protein kinase A activity, and ADORA1 gene expression, indicating a possible causal relationship. The intracellular level of Ca(2+) was unaffected even by high concentrations of caffeine. Protein expressions demonstrated two main targets for caffeine-ADORA1 and ADORA2A.
  
  
  CONCLUSIONS
  A physiological high dose of caffeine inhibits PTH secretion in human parathyroid cells, possibly due to a decrease of the intracellular level of cAMP. The observation demonstrates a functional link between caffeine and parathyroid cell function.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 76 Stockholm, Sweden. ming.lu@ki.se
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Lars-Ove
authors.initials: LO
authors.lastname: Farnebo
authors.forename: Robert
authors.initials: R
authors.lastname: Bränström
authors.forename: Catharina
authors.initials: C
authors.lastname: Larsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000032:analysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000032:analysis / Q000235:genetics
chemical_list: D010281:Parathyroid Hormone; D018047:Receptors, Purinergic P1; D002110:Caffeine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium