Histamine and human parathyroid adenoma: effect on adenosine 3',5'-monophosphate accumulation in vitro

We studied in vitro the presence of histamine and the effect of histamine and its antagonists on cAMP accumulation in parathyroid tissue (parathyroid adenoma or hyperplasia) from patients with primary hyperparathyroidism. Parathyroid adenomatous tissue contained 11.2 +/- 2.9 ng histamine/g wet weight (approximately 2 X 10(-5) M), as determined by a specific radioenzyme assay. Histamine caused a prominent increase in cAMP accumulation in parathyroid tissue slices in a dose-dependent manner, with half-maximal stimulation being achieved at 5 X 10(-6) M and maximal stimulation occurring at 10(-4) M histamine. The histamine H2 receptor antagonists, cimetidine and metiamide, caused profound inhibition of histamine-stimulated cAMP accumulation in the parathyroid tissue. Pyrilamine, an H1 antagonist, also inhibited histamine-stimulated cAMP accumulation. Isoproterenol, a beta-adrenergic agonist, elicited marked elevation of cAMP, and its stimulatory effect was blocked by propranolol, but the effects of histamine on cAMP levels in parathyroid tissue were not blocked by propranolol. Histamine significantly stimulated (an increase of 50%) the release of immunoreactive parathyroid hormone. The present observations demonstrate that parathyroid adenomatous tissue has a relatively high content of histamine, and the release of immunoreactive parathyroid hormone from this tissue. The effects of antagonists suggest that histamine stimulates cAMP accumulation in the parathyroid adenomatous tissue by an action on both H2 and H1 histamine receptors.