Histamine stimulation and inhibition of human cryopreserved parathyroid tissue

To elucidate the mechanism by which cimetidine, an H2 antagonist, inhibits parathormone secretion, immunoreactive cyclic AMP (cAMP) production was measured at low (0.5 mM) and normal (1.0 mM) calcium concentrations, with histamine stimulation and histamine inhibition by cimetidine, in a cell dispersion preparation from cryopreserved glands of 12 hyperparathyroid patients. At low calcium, histamine-mediated cAMP production increased from a basal level of 382 +/- 44 femtomoles/10(5) cells to 514 +/- 74 femtomoles/10(5) cells (P less than 0.05). Cimetidine inhibition of histamine-stimulated parathyroid cells at low calcium resulted in a decrease in cAMP production from 514 +/- 74 femtomoles/10(5) cells to 410 +/- 62 femtomoles/10(5) cells (P less than 0.01). At normal calcium the cAMP production in the histamine-stimulated experiment increased from a basal level of 293 +/- 66 femtomoles/10(5) cells to 477 +/- 100 femtomoles/10(5) cells (P less than 0.01) and decreased to 321 +/- 69 femtomoles/10(5) cells (P less than 0.01) in the histamine and cimetidine experiment. Stimulation by isoproterenol, a beta-adrenergic agonist, at low calcium in the histamine-primed group showed an increase in cAMP production from 514 +/- 74 femtomoles/10(5) cells to 639 +/- 71 femtomoles/10(5) cells (P less than 0.005). These results suggest that histamine plays an important role in cAMP production in hyperparathyroid cells and that cimetidine inhibition of histamine-stimulated cAMP production may explain the decrease of immunoreactive parathormone by this H2 antagonist reported in patients with hyperparathyroidism.