Abstract
The effects of histamine on cAMP accumulation and parathyroid hormone (PTH) release were studied in dispersed cell preparations from pathological parathyroid tissue of 13 patients with parimary hyperparathyroidism. Histamine stimulated cAMP accumulation 1.4- to 110-fold in a dose- and time-dependent manner. The increased cAMP content was inhibited by the H2 antiagonist, cimetidine and the H1 antagonist, promethazine, with Ki values of 0.14-0.46 and 0.2-0.37 .mu.M, respectively. Moreover, in one cell preparation, the H2 agonist, dimaprit, stimulated cAMP accumulation 2- to 3-fold, while the H1 agonist, 2-pyridylethylamine, had no effect on cAMP levels. The potenti .alpha.-and .beta.-adrenergic antagonists, phentolamine and propranolol, did not inhibit histamine-stimulated cAMP accumulation significantly. Histamine also caused a dose- and time-dependent increase in PTH release, with a Ka in reasonable agreement with that for cAMP accumulation (0.5-1 vs. 3 .mu.M, respectively); this indicates that enhanced cAMP accumulation was linked to increased secretion. Evidently pathological human parathyroid cells have histamine receptors, probably H2 in subtype, which mediate enhanced cAMP accumulation and PTH release.