Subject(s)
Anesthetics, Local/pharmacology , Propranolol/pharmacology , Receptors, Cell Surface/drug effects , Thyrotropin/metabolism , Adrenergic beta-Antagonists/pharmacology , Cell Membrane/metabolism , Humans , Kinetics , Membrane Lipids/metabolism , Receptors, Cell Surface/metabolism , Structure-Activity Relationship , Thyroid Gland/metabolismSubject(s)
Adenylyl Cyclases/metabolism , Anesthetics, Local/pharmacology , Receptors, Cell Surface/metabolism , Thyroid Gland/metabolism , Thyrotropin/metabolism , Humans , Metoprolol/pharmacology , Polyphloretin Phosphate/pharmacology , Practolol/pharmacology , Propranolol/pharmacology , Quinidine/pharmacology , Receptors, Cell Surface/drug effects , Thyroid Gland/drug effects , Thyrotropin/pharmacologyABSTRACT
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.
Subject(s)
Adenylyl Cyclases/metabolism , Propranolol/pharmacology , Thyroid Gland/enzymology , Thyrotropin/physiology , Adenosine Triphosphatases/metabolism , Anesthetics, Local/pharmacology , Animals , Cattle , Cell Membrane/drug effects , Cell Membrane/enzymology , Enzyme Activation/drug effects , Fluorides/pharmacology , In Vitro Techniques , Lidocaine/pharmacology , Magnesium/pharmacology , Phosphoric Monoester Hydrolases/metabolism , Potassium/pharmacology , Practolol/pharmacology , Prostaglandins E/pharmacology , Quinidine/pharmacology , Sodium/pharmacology , Stereoisomerism , Thyrotropin/pharmacologyABSTRACT
Catecholamine stimulation of adenyl cyclase activity associated with bovine subcellular fractions enriched in plasma membranes is described. The relative potencies of isoproterenol (IPNA), epinephrine (E), and norepinephrine (NE) were 4.7:1.0:0.02, which is characteristic for a beta-adrenergic receptor system. Stimulation with IPNA (5 times 10- minus 6 M) was inhibited by propranolol. The inhibition was stereospecific for the L-isomer of propranolol and a concentration as low as 2 times 10- minus 8 M was required to effect 50% inhibition. Both these observations, and the competitive kinetics of inhibition which applied to the system, confirmed the classification of a beta-adrenergic receptor system. Phentolamine, an alpha-antagonist, also inhibited IPNA stimulation, although high doses (5 times 10- minus M) were required to cause total inhibition. Inhibition was also observed with quinidine (1 mM) and lignocaine (10- minus 2 M).
