Studies on Inhibition of TSH Stimulation of Adenyl Cyclase Activity in Thyroid Plasma Membrane Preparations by Propranolol

Abstract

Propranolol (1 mM) was found to inhibit TSH stimulation of adenyl cyclase activity in a subcellular fraction from bovine thyroid enriched in plasma membranes. However, stimulation due to PGE1 or NaF was not similarly inhibited. Since (i) and inhibition was observed at concentrations of propranolol between 10-minus 4 and 10- minus 3M, and appeared to be noncompetitive (ii) the optical isomers of propranolol were equipotent, (iii) inhibition was specific for propranolol since it was not observed with the closely related drug practolol (1 mM), and (iv) quinidine (1 mM) and the local anaesthetics lignocaine and aptocaine also proved inhibitory, we concluded that propranolol inhibition of TSH stimulation was due to its "quinidine-like" properties (i.e., relatively specific and characteristic membrane-active properties) and not to its action as a beta-adrenergic antagonist.

Cyclic AMP release from normal human thyroid slices in response to thyrotrophin

“…Ademlate cycla.se activity of human thyroid membranes Stimulation by TSH or NaF of adenylate cyclase activity in thvroid membrane prepatations was effected as des¬ cribed previously (Marshall et al 1975). TSH and NaF were added to membranes (2 mg protein/ml) in the presence of 2.5 mvt ATP, 5 mM Mg+ + .…”

Catecholamine stimulation of cyclic AMP and progesterone production in rat corpora lutea of different ages

“…Higher concentrations of propranolol could inhibit also the effects of LH. Higher concentrations, however, do exert quinidine like effects (Marshall et al 1975). The inhibitory effect of high concentrations of propranolol on the production of cAMP and pro¬ gesterone is most likely attributable to this unspecific effect of the drug.…”

Preparation of Radiolabeled Thyroid-Stimulating Immunoglobulins (TSI) by Recombining TSI Heavy Chains with125I-Labeled Light Chains: Direct Evidence That the Product Binds to the Membrane Thyrotropin Receptor and Stimulates Adenylate Cyclase

“…Adenylate cyclase activity was determined by measurement of the quantity of cAMP generated from ATP during incubation of human thyroid membrane with the appropriate stimulator (12). Approximately 50 jug thyroid membranes in 50 /xl 25 mM Tris-HCl buffer, pH 7.4, were added to tubes containing 2.5 mM ATP, 5 mM MgCl 2 , 10 mM theophylline, 10 mM phosphoenolpyruvate, and 20 Hg pyruvate kinase.…”