guanylyl-imidodiphosphate and Parathyroid-Neoplasms

To examine whether alterations in parathyroid adenylate cyclase might be associated with glandular hyperfunction, we compared enzyme activity in membranes from 7 normal glands with activity from 18 abnormal and 5 noninvolved glands from patients with primary hyperparathyroidism. Compared with the normal glands, the specific enzyme activity after full stimulation with guanyl-5'yl imidodiphosphate was significantly decreased in both hyperplastic and noninvolved glands from the hyperparathyroid subjects. While the enzyme activity of all tissues could be suppressed by calcium, a twofold higher calcium concentration was required for comparable suppression of the enzyme from adenomas as compared with normal or noninvolved glands. Alterations in the adenylate cyclase complex of hyperplastic parathyroid glands may explain, in part, the elevated "set point" for calcium homeostasis in primary hyperparathyroidism.

Topics: Adenoma; Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Adult; Aged; Calcimycin; Calcium; Child; Dose-Response Relationship, Drug; Female; Guanylyl Imidodiphosphate; Humans; Hyperparathyroidism; In Vitro Techniques; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms

Recent evidence suggests that the histamine receptor blocking agent cimetidine can decrease parathyroid hormone release from human parathyroids. To determine the mechanism for inhibition we examined the ability of histamine 1 X 10(-5) moles/liter to stimulate adenylate cyclase in a particulate membrane preparation from 13 human parathyroid glands. Histamine significantly increased adenylate cyclase activity as compared to control; however, the degree of stimulation was variable among the individual tissue samples. Enzyme stimulation was dose dependent over the concentration range of 1 X 10(-7) to 1 X 10(-4) moles/liter. Cimetidine at 1 X 10(-4) moles/liter completely abolished the histamine mediated increase in activity, but did not block the epinephrine-induced stimulation. The identification of an adenylate cyclase system in certain human parathyroid adenomas that is stimulated by histamine and blocked by cimetidine may offer a basis for the pharmacologic alteration of parathyroid hormone secretion.

Topics: Adenoma; Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Cimetidine; Dose-Response Relationship, Drug; Enzyme Activation; Epinephrine; Guanidines; Guanylyl Imidodiphosphate; Histamine; Humans; Parathyroid Neoplasms; Sodium Fluoride