thiourea and Hyperparathyroidism

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 primary 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 antagonist cimetidine and the H1 antagonist promethazine, with Ki values of 0.14--0.46 and 0.2--0.37 micrometer, 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 potent 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 micrometer, respectively), indicating that enhanced cAMP accumulation was linked to increased secretion. These results indicate that pathological human parathyroid cells have histamine receptors, probably H2 in subtype, which mediate enhanced cAMP accumulation and PTH release.

Topics: Cyclic AMP; Dimaprit; Dose-Response Relationship, Drug; Histamine; Histamine Antagonists; Humans; Hyperparathyroidism; In Vitro Techniques; Parathyroid Glands; Parathyroid Hormone; Receptors, Histamine H2; Thiourea