Biomaterial Database

Decreased myocardial adenyl cyclase activity in hypothyroidism. 1969

G S Levey, and C L Skelton, and S E Epstein

It has been suggested that hypothyroidism may alter the responsiveness of the heart to sympathetic stimulation. To define more precisely the interrelationship between hypothyroidism and catecholamine responsiveness we: (a) studied the effects of norepinephrine and fluoride on the activation of adenyl cyclase in the particulate fraction of heart homogenates from euthyroid and hypothyroid cats; and (b) assessed the contractile response of isolated right ventricular papillary muscles from the same cats to increasing concentrations of norepinephrine. It was found that maximal accumulation of cyclic 3',5'-adenosine monophosphate (3',5'-AMP) was significantly lower at peak norepinephrine concentrations in the hypothyroid (284 +/-5 pmoles) than in the euthyroid group (326 +/-10 pmoles) (P < 0.02). However, the K(m) for norepinephrine was similar in both groups (1-2 x 10(-5) moles/liter), and there was no apparent change in the threshold concentration. Fluoride-mediated increases in Cyclic 3',5'-AMP accumulation were also significantly lower in the hypothyroid (585 +/-25 pmoles) as compared to the euthyroid group (790 +/-20 pmoles) (P < 0.02). In contrast, norepinephrine produced a similar augmentation of contractility in isolated papillary muscles from the hypothyroid and euthyroid cats. It thus appears that although the hypothyroid state is associated with a decrease in the total amount of myocardial adenyl cyclase per milligram of tissue capable of being activated by norepinephrine or fluoride, there is no change in the sensitivity of the enzyme to norepinephrine stimulation. Moreover, the finding that the inotropic response to norepinephrine is unaltered in hypothyroidism is compatible with the hypothesis that only a fraction of the total intracellular cyclic 3',5'-AMP produced by norepinephrine activation of adenyl cyclase is required to elicit the inotropic response.

UI	MeSH Term	Description	Entries
D007037	Hypothyroidism	A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.	Central Hypothyroidism,Primary Hypothyroidism,Secondary Hypothyroidism,TSH Deficiency,Thyroid-Stimulating Hormone Deficiency,Central Hypothyroidisms,Deficiency, TSH,Deficiency, Thyroid-Stimulating Hormone,Hormone Deficiency, Thyroid-Stimulating,Hypothyroidism, Central,Hypothyroidism, Primary,Hypothyroidism, Secondary,Hypothyroidisms,Primary Hypothyroidisms,Secondary Hypothyroidisms,TSH Deficiencies,Thyroid Stimulating Hormone Deficiency,Thyroid-Stimulating Hormone Deficiencies
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D009638	Norepinephrine	Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic.	Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010210	Papillary Muscles	Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae.	Muscle, Papillary,Muscles, Papillary,Papillary Muscle
D010744	Phosphoric Monoester Hydrolases	A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate.	Phosphatase,Phosphatases,Phosphohydrolase,Phosphohydrolases,Phosphomonoesterase,Phosphomonoesterases,Phosphoric Monoester Hydrolase,Hydrolase, Phosphoric Monoester,Hydrolases, Phosphoric Monoester,Monoester Hydrolase, Phosphoric
D002415	Cats	The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)	Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D004798	Enzymes	Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.	Biocatalyst,Enzyme,Biocatalysts
D005459	Fluorides	Inorganic salts of hydrofluoric acid, HF, in which the fluorine atom is in the -1 oxidation state. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Sodium and stannous salts are commonly used in dentifrices.	Fluoride