The Influence of Adrenergic Receptor Blocking Agents on the Mouse Thyroid

1970 ◽  
Vol 39 (6) ◽  
pp. 781-791 ◽  
Author(s):  
Pat Kendall-Taylor ◽  
D. S. Munro
Keyword(s):  
Adrenergic Receptor ◽  
Adenosine Monophosphate ◽  
Thyroid Stimulating Hormone ◽  
Adrenergic Blockade ◽  
Blocking Drug ◽  
Receptor Blocking ◽  
Long Acting ◽  
Adrenergic Blocking ◽  
Mouse Thyroid

1. The influence of adrenergic receptor blocking drugs on the mouse thyroid gland maintained in vitro has been investigated. 2. Phentolamine, an α adrenergic blocking drug, and propranolol, a β blocking drug, inhibited the release of [131I]iodothyronines from pre-labelled mouse thyroids, which otherwise occurred when the glands were incubated in the presence of thyroid stimulating hormone, long acting thyroid stimulator, or cyclic 3′5′-adenosine monophosphate. 3. Evidence is presented to show that (a) the inhibition is not due to adrenergic blockade, (b) the effect cannot wholly be attributed to the prevention of adenyl cyclase activation, (c) the mechanism of action of the two drugs is dissimilar. 4. The observed clinical response in the treatment of thyrotoxicosis does not appear to be related to this antithyroid effect of propranolol.

THE ACTION OF DIBUTYRYL CYCLIC 3′,5′-ADENOSINE MONOPHOSPHATE ON THE MOUSE THYROID GLAND IN VITRO

1970 ◽  
Vol 47 (3) ◽  
pp. 333-338 ◽  
Author(s):  
PAT KENDALL-TAYLOR ◽  
D. S. MUNRO
Keyword(s):  
Thyroid Gland ◽  
Thin Layer ◽  
Thin Layer Chromatography ◽  
Adenosine Monophosphate ◽  
Thyroid Stimulating Hormone ◽  
In Vitro Assay ◽  
Vitro Assay ◽  
Layer Chromatography ◽  
Mouse Thyroid

SUMMARY The effects of dibutyryl cyclic 3′,5′-adenosine monophosphate (DBc-AMP) on the mouse thyroid gland have been investigated in the in-vitro assay of Brown & Munro (1967). The distribution of 131I-labelled compounds in the glands and the supporting medium have been analysed by thin-layer chromatography and the changes induced by cyclic 3′,5′-adenosine monophosphate (c-AMP), DBc-AMP or thyroid-stimulating hormone (TSH) compared. The release of 131I was increased when the glands were incubated with DBc-AMP, c-AMP or TSH. The potency of DBc-AMP was approximately 50 times that of c-AMP on a basis of molarity. Like TSH, DBc-AMP increased the proportion of iodothyronines in the system as a whole, whereas c-AMP had little effect. The possible explanations for this are discussed.

A COMPARISON OF THE IN-VITRO ACTIONS OF THYROID-STIMULATING HORMONE AND CYCLIC 3′,5′-ADENOSINE MONOPHOSPHATE ON THE MOUSE THYROID GLAND

1969 ◽  
Vol 43 (3) ◽  
pp. 477-485 ◽  
Author(s):  
JANICE M. ENSOR ◽  
D. S. MUNRO
Keyword(s):  
Cyclic Amp ◽  
Culture Medium ◽  
Adenosine Monophosphate ◽  
Thyroid Stimulating Hormone ◽  
Vitro Assay ◽  
Thyroid Glands ◽  
Influence Of Tsh ◽  
Mouse Thyroid ◽  
Stimulating Hormone

SUMMARY In the in-vitro assay of Brown & Munro (1967) thyroid-stimulating hormone (TSH) increased the release of radioactive iodine from mouse thyroid glands labelled with 131i during life. Paper chromatography showed that TSH increased the 131I-labelling of thyroxine and tri-iodothyronine both in the culture medium and in hydrolysates of the thyroids. Cyclic 3′,5′-adenosine monophosphate (cyclic AMP) also increased 131I release in this assay and increased the 131I-labelling of thyronines in the culture medium. The effects on thyroid hydrolysates were less striking. Theophylline potentiated the influence of TSH and cyclic AMP in the assay and, by itself, increased 131I release and the labelling of iodothyronines in the thyroid without altering the distribution of 131I in the culture medium. The implications of these results are discussed.

A NEW IN VITRO ASSAY FOR THYROIDSTIMULATING HORMONE

1967 ◽  
Vol 38 (4) ◽  
pp. 439-449 ◽  
Author(s):  
JILL BROWN ◽  
D. S. MUNRO
Keyword(s):  
Radioactive Iodine ◽  
Thyroid Stimulating Hormone ◽  
Vitro Assay ◽  
Line Parallel ◽  
Thyroid Glands ◽  
Long Acting ◽  
Response Line ◽  
Mouse Thyroid

SUMMARY A new in vitro assay for thyroid-stimulating hormone (TSH) is described. The parameter of TSH action is the discharge of radioactive iodine from mouse thyroid glands labelled with 131I in vivo. The assay is sensitive to human TSH and gave consistent results during 1 yr. without seasonal variation. A potent preparation of long-acting thyroid stimulator gave a dose-response line parallel with human TSH. Fresh human serum was toxic to the assay preparation so that circulating TSH levels cannot be measured.

scholarly journals The beta-adrenergic receptor adenylate cyclase complex of Rauscher murine erythroleukemia cells and its response to erythropoietin-induced differentiation

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 84-90 ◽  
Author(s):  
AJ Sytkowski ◽  
CJ Kessler
Keyword(s):  
Adenylate Cyclase ◽  
Adrenergic Receptor ◽  
Developmental Process ◽  
Adenosine Monophosphate ◽  
Beta Adrenergic Receptor ◽  
Beta Adrenergic ◽  
Erythroleukemia Cells ◽  
Murine Erythroleukemia ◽  
Murine Erythroleukemia Cells

Abstract Rauscher murine erythroleukemia cells, grown continuously in vitro, undergo erythroid differentiation in response to the hormone erythropoietin. Therefore, they serve as an important model system with which to examine critical biochemical aspects of this developmental process. Intact, uninduced Rauscher cells possess a functional beta- adrenergic receptor-adenylate cyclase complex. The adrenergic agonists, isoproterenol, epinephrine, and norepinephrine, exhibited activation constants (Kact) of 0.1, 0.5, and 20 mumol/L, respectively. Thus, the beta-receptor-cyclase complex of Rauscher cells is apparently one of the most sensitive of all erythroid cells reported thus far. The epinephrine-stimulated cyclic adenosine monophosphate (cAMP) response was inhibited by propranolol, alprenolol, and hydroxybenzylpindolol, with inhibition constants (KI) of 3.8, 2.2, and 0.1 nmol/L, respectively. Using [125I]-iodohydroxybenzylpindolol as ligand, uninduced Rauscher cells were shown to possess 1,100 receptors/cell, with an equilibrium dissociation constant (KD) of 400 pmol/L. Erythropoietin, but not dimethylsulfoxide, induction caused a specific increase in receptor density to 3,300/cell on differentiating Rauscher cells. This is the first demonstration of membrane receptor regulation by erythropoietin that may be important in the complex interplay of hormonal effects during erythropoiesis.

IN VITRO EFFECTS OF LATS AND TSH ON PHOSPHODIESTERASE ACTIVITY IN HUMAN THYROID HOMOGENATES

1971 ◽  
Vol 67 (2) ◽  
pp. 209-215 ◽  
Author(s):  
K. Miyai ◽  
N. Amino ◽  
M. Azukizawa ◽  
Y. Kumahara
Keyword(s):  
Enzyme Activity ◽  
Adenosine Monophosphate ◽  
Human Thyroid ◽  
Phosphodiesterase Activity ◽  
Significant Difference ◽  
In Vitro Effects ◽  
Long Acting ◽  
Bovine Tsh

ABSTRACT The in vitro effects of long-acting thyroid stimulator (LATS) and thyrotrophin (TSH) on phosphodiesterase activity in human thyroid homogenates were studied. The enzyme activity was estimated by the destruction of 3H-cyclic 3′,5′-adenosine monophosphate. Bovine TSH had no effect on the enzyme activity. Five experiments were carried out using different batches of LATS-IgG and normal IgG which were preincubated with thyroid homogenates or not. There was no significant difference between the enzyme activity with LATS-IgG and that with normal IgG, while the activity was mostly inhibited by theophylline. These data are not consistent with the hypothesis that LATS acts as an antibody to phosphodiesterase.

THE EFFECTS OF GR32191, A NEW THROMBOXANE RECEPTOR BLOCKING DRUG,ON PLATELETS AND VASCULAR SMOOTH MUSCLE IN VITRO

1987 ◽  
Author(s):  
P Lumley ◽  
E W Collington ◽  
P Hallett ◽  
E J Hornby ◽  
p PA Humphrey ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Vascular Smooth Muscle ◽  
Inhibitory Activity ◽  
Whole Blood ◽  
Blocking Drug ◽  
Receptor Blocking ◽  
Thromboxane Receptor ◽  
Induced Aggregation

The effect of a new thromboxane receptor blocking drug GR32191 ([1R-[1α(Z),2β,3β,5α]]-(+)-7-[5-[[(1,1"-biphenyl)-4-yl]methoxy] -3-hydroxy-2-(l-piperidinyl)cyclopentyl]-4-heptenoic acid,hydrochloride) has been examined upon platelets and vascular smooth muscle. In human platelet-rich plasma (PRP), aggregation to thromboxane(Tx) A2, PGH2, arachidonic acid, collagen andU-46619 was antagonised by GR32191 (IC50 range 2-36 nM).Primary aggregation (PRP treated with aspirin 10 pM) to ADP, 5-HT and adrenaline were unaffected by concentrations of GR32191 up to 10 pM. In human PRP, U-46619-induced aggregation and 5-HT release were antagonised by GR32191(10-100 nM). In contrast, in theabsence of aspirin, ADP-induced 5-HT release,but not aggregation, was antagonised by the compound implicating a role for TXA2 in the release process. In human PRP GR32191 (up to 30μM) did not itself induce aggregation or, in the presence of EGTA (4 mM), induce detectable shape change. Up to 10 μM GR32191 was without effect upon the inhibitory activity of PGI2 or PGD2 and at 1μMhad no significant inhibitory activity upon fatty acid cyclooxygenase, thromboxane synthase, prostacyclin synthase, 12-lipoxygenase orphosphodiesterase. The effect of GR32191was quantified further in human platelets suspended in whole blood or physiological salt solution. Aggregation to U-46619 was antagonised byGR32191 with a pA2 (slope of the Schild regression) of 8.2 (1.3) in whole blood and 8.8 (1.3) in resuspended platelets. The compound competitively and specifically antagonised the contractions of strips of human isolatedpulmonary blood vessels and rat and guinea-pig aortic strips produced by U-46619 with pA2 (slope) values of 8.2 (1.1), 7.9 (0.9) and 8.7(0.9) respectively. In contrast contractions induced by KC1 and 5-HT (rat) orKC1and histamine (guinea-pig) were unaffectedbyconcentrations of GR32191 up to 30 μM.Thus GR32191 is a potent and specific thromboxane receptor blocking drug on platelets and vascular smooth muscle in vitro. It is orally active and long lasting in man (Thomas, M et al.,this meeting).

Stimulation of thyroidal iodothyronine 5'-monodeiodinase by long-acting thyroid stimulator (LATS)

1987 ◽  
Vol 114 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Sing-Yung Wu ◽  
R. Reggio ◽  
W. Florsheim ◽  
I. J. Chopra ◽  
D. H. Solomon
Keyword(s):  
Marked Reduction ◽  
Maximum Velocity ◽  
Normal Serum ◽  
Detectable Change ◽  
Thyroid Glands ◽  
Long Acting ◽  
Insight Into ◽  
Stimulation Of ◽  
Mouse Thyroid

Abstract. To evaluate the effect of long-acting thyroid stimulator (LATS) on thyroid iodothyronine monodeiodinating activity, we have studied the in vitro conversion of T4 to T3 by mouse thyroid homogenate comparing tissue from LATS treated (0.1 ml LATS(+) serum, ip, for 3 days) with tissues from LATS(–) Graves' disease patients' serum or normal serum treated controls. Five out of seven LATS(+) sera were shown to stimulate the T4 5'-deiodinase significantly in mouse thyroid. There was no significant correlation between LATS titre and deiodinase activities in the different sera tested. To compare the effect of LATS and TSH (0.2 IU, ip daily), studies were carried out from 12 to 72 h. LATS had a similar latency of 12 h on the stimulation of thyroid deiodinase compared to TSH as reported earlier. However, the conversion activities reached a plateau by 12 h after LATS treatment, while it continued to rise upon daily TSH injection from 24 to 72 h. In addition, TSH caused a marked reduction of thyroid protein and an early peaking in serum T3 and T4 at 12 h, whereas LATS caused no detectable change in thyroid protein and a gradual rise in circulating T3 and T4. The kinetic analysis indicated that LATS-mediated stimulation of T4 5'-deiodinase was, similar to TSH, associated with an increase in maximum velocity (Vmax were 139, 208 and 505 pmol/mg protein/30 min respectively in control, LATS and TSH-treated animals) without a demonstrable change in the apparent Km (approximately 2.0 μm for T4). The present study demonstrated that some LATS-rich sera stimulate thyroid T4 to T3 conversion in mouse. It provides an insight into the mechanism of increased T3 secretion from Graves' thyroid glands.

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