Changes in the cyclic nucleotides (cCMP, cAMP and cGMP) of rat thyroid induced by prolonged administration of LATS and TSH

1981 ◽  
Vol 98 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Yukio Ochi ◽  
Shiro Hosoda ◽  
Takashi Hachiya ◽  
Manabu Yoshimura ◽  
Tadayoshi Miyazaki ◽  
...  

Abstract. It has recently been suggested that cyclic CMP (cCMP) has a physiological role in cell function. In this study, we examined the content of cCMP, cAMP & cGMP and each hydrolyzing enzyme (phosphodiesterase, (PDE)) in rat thyroid during administration of LATS and TSH for 7 days (Exp. 1), and also in the thyroid of rats given methylthiouracil (MTU) for 4 months (Exp. 2). Each cyclic nucleotide was determined by RIA, and PDE activity was determined according to Kuo's method. Exp. 1: the wet weight of thyroid in the LATS and TSH group increased 3 and 2 times respectively, from the control. Both the LATS and TSH groups showed increased plasma T4 and T3 levels. In both groups the cAMP content per wet weight of thyroid was increased slightly, but cGMP content did not change. In contrast, the cCMP content decreased markedly. Both the LATS and TSH groups showed an increase of cAMP-PDE activity in the thyroid, and no change of cGMP-PDE, while cCMP-PDE decreased markedly. In all groups levels of these 3 cyclic nucleotides and PDE activities in plasma were unaffected. Exp. 2: in the MTU group the thyroid weight increased 4.5 times over the control, and plasma T4 and T3 levels were extremely low. The cAMP content in whole thyroid gland and also per mg wet weight was increased markedly, but cGMP content did not change. cCMP content decreased significantly. The plasma cAMP level increased slightly, but the plasma cGMP and cCMP levels did not change. The increase of cAMP content and cAMP-PDE activity, and conversely the decrease of cCMP content and cCMP-PDE in the thyroid by LATS and TSH stimulation, suggest that cCMP may play a physiologically important role within the cells, similar to cAMP in the mechanism of hormone action.

1978 ◽  
Vol 88 (4) ◽  
pp. 713-720 ◽  
Author(s):  
Yukio Ochi ◽  
Shiro Hosoda ◽  
Takashi Hachiya ◽  
Yoshihiro Kajita ◽  
Manabu Yoshimura ◽  
...  

ABSTRACT The effects of LATS and TSH on the cyclic nucleotide content and enzymatic activity in rat thyroid was observed during the continuous administration of LATS or TSH for 6 days. Serum T4 and T3 levels were increased significantly compared with the saline controls. The cyclic nucleotide (cAMP and cGMP) levels and enzyme activities per wet weight of tissue were determined. The thyroid weight in both the LATS and TSH groups increased approximately two-fold, but cAMP and cGMP content per wet weight did not significantly change. Neither cyclic nucleotide showed any significant change in plasma. The cAMP-PDE activity in the thyroid significantly increased in both the LATS and TSH groups, but the cGMP-PDE activity was unchanged. Neither was cyclic nucleotide-PDE activity changed in the plasma. The ATPase activity in the thyroid increased markedly in both the LATS and TSH groups, while 5′-nucleotidase activity did not change. These data suggest that LATS and TSH appear to have a stimulatory effect on the metabolism of cAMP, but do not affect the metabolism of cGMP.


1990 ◽  
Vol 68 (10) ◽  
pp. 1357-1362
Author(s):  
Russell F. Husted ◽  
Gerard P. Clancy ◽  
Abigail Adams-Brotherton ◽  
John B. Stokes

The adenosine analogue 2-chloroadenosine (2-CA) is often used to determine the biologic effects of adenosine because 2-CA is less susceptible to degradation than adenosine. We studied the effects of 2-CA on primary cultures of rat inner medullary collecting ducts because there is good evidence that adenosine can influence cell function through its effects on second messengers. 2-CA inhibited Na+ transport across the apical membrane and increased cAMP content of the cells. The major adenosine receptors in these cells appear to be the stimulatory (A2) type. Stimulation of cAMP by 2-CA was more potent when applied to the apical membrane than to the basolateral membrane, an effect opposite to that of vasopressin. These results imply that adenosine receptors are more numerous or more effective on the apical membrane than on the basolateral membrane. Inhibition of Na+ transport was probably not mediated by an adenosine receptor as evidenced by (i) a lack of effect of adenosine and other adenosine analogues on Na+ transport; (ii) a lack of effect of nonmetabolizable cyclic nucleotides on Na+ transport; and (iii) a clear discrepancy in the temporal course of 2-CA effects on a second messenger system (cAMP) and 2-CA inhibition of Na+ transport. Dipyridimole, an inhibitor of adenosine transport, also reduced Na+ transport. Taken together, the data suggest that 2-CA inhibits Na+ transport by interfering with adenosine transport or metabolism.Key words: cAMP, cGMP, 2-chloroadenosine, vasopressin, Na+ transport, dipyridimole, adenosine metabolism.


1991 ◽  
Vol 260 (5) ◽  
pp. G764-G769 ◽  
Author(s):  
S. Rattan ◽  
C. Moummi ◽  
S. Chakder

This investigation examined and compared the role of cyclic nucleotides in the mediation of internal anal sphincter (IAS) relaxation caused by the addition of neuropeptide calcitonin gene-related peptide (CGRP) and atrial natriuretic factor (ANF). The studies were performed in vitro on smooth muscle strips of opossum IAS. The relaxation produced by CGRP and ANF was examined before and after the addition of tetrodotoxin (TTX) (1 x 10(-6)M). At this concentration, TTX did not have any significant effect on the relaxation produced by either CGRP or ANF, suggesting that these peptides act directly on the smooth muscle. Addition of CGRP (3 x 10(-6) M) produced the maximal relaxation and significantly increased cAMP content without changing cGMP. On the other hand, addition of ANF (3 x 10(-6) M) caused a similar fall in IAS tension that was accompanied by a significant elevation in cGMP without any change in cAMP content. The rises in the levels of cyclic nucleotides preceded the onset of fall in the resting tension of IAS. Our results demonstrate that CGRP and ANF relax isolated strips of opossum IAS by their action directly at the smooth muscle and that this relaxation is associated with an increase in cAMP and cGMP, respectively. The studies suggest the presence of both cAMP and cGMP pathways in the IAS and that the relaxation of IAS smooth muscle in response to different peptides may occur via a specific intracellular biochemical pathway.


1981 ◽  
Vol 59 (4) ◽  
pp. 329-334 ◽  
Author(s):  
Uma Srivastava ◽  
Mikael Sebag ◽  
Manohar Thakur

cAMP and cGMP contents were determined in the skeletal and cardiac muscle of normal and dystrophic mice. cAMP content increased in the dystrophic muscle at every stage of the disease whereas cGMP content decreased in the preliminary stages and increased at the terminal stage of the disease. The content of both nucleotides per heart was not affected in murine dystrophy. Thus, levels of cyclic nucleotides appear to be selectively altered in dystrophic skeletal muscle.


2011 ◽  
Vol 11 (S1) ◽  
Author(s):  
Katharina Werner ◽  
Frank Schwede ◽  
Hans-Gottfried Genieser ◽  
Jörg Geiger ◽  
Elke Butt

2020 ◽  
Vol 48 (19) ◽  
pp. 10648-10661 ◽  
Author(s):  
Anna Constance Vind ◽  
Aitana Victoria Genzor ◽  
Simon Bekker-Jensen

Abstract Cells rely on stress response pathways to uphold cellular homeostasis and limit the negative effects of harmful environmental stimuli. The stress- and mitogen-activated protein (MAP) kinases, p38 and JNK, are at the nexus of numerous stress responses, among these the ribotoxic stress response (RSR). Ribosomal impairment is detrimental to cell function as it disrupts protein synthesis, increase inflammatory signaling and, if unresolved, lead to cell death. In this review, we offer a general overview of the three main translation surveillance pathways; the RSR, Ribosome-associated Quality Control (RQC) and the Integrated Stress Response (ISR). We highlight recent advances made in defining activation mechanisms for these pathways and discuss their commonalities and differences. Finally, we reflect on the physiological role of the RSR and consider the therapeutic potential of targeting the sensing kinase ZAKα for treatment of ribotoxin exposure.


1994 ◽  
Vol 266 (4) ◽  
pp. H1494-H1501 ◽  
Author(s):  
H. Parfenova ◽  
M. Shibata ◽  
S. Zuckerman ◽  
C. W. Leffler

The role of cyclic nucleotides and prostanoids in cerebrovascular reactivity to increased carbon dioxide was investigated in anesthetized and artificially ventilated newborn pigs equipped with closed cranial windows. Pial arteriolar diameter was measured, and cortical periarachnoid cerebrospinal fluid (CSF) was collected from beneath the cranial window for determination of adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), and prostanoids. Progressively increasing arterial PCO2 (PaCO2) from normocapnia (33 +/- 1 mmHg) to hypercapnia (final PaCO2, 83 +/- 2 mmHg) resulted in dose-dependent pial arteriolar dilation and concomitant increases in cAMP, cGMP, and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in cortical CSF. N omega-methyl-L-arginine, N omega-nitro-L-arginine, N omega-nitro-L-arginine methyl ester, methylene blue, and LY 83583 did not inhibit cerebral vasodilation or the increases in cortical cAMP/cGMP induced by hypercapnia. Indomethacin abolished the vasodilatory response to hypercapnia and attenuated the hypercapnia-induced increases in cAMP and cGMP. Prostacyclin analogues increased both cAMP and cGMP levels in cortical CSF and induced pial arteriolar dilation (iloprost > carbaprostacyclin). The present data suggest that in newborn pigs cyclic nucleotides are involved in cerebral vasodilation in response to hypercapnia via a prostanoid-dependent mechanism.


1985 ◽  
Vol 248 (5) ◽  
pp. H745-H749 ◽  
Author(s):  
G. Bkaily ◽  
N. Sperelakis

The role of guanosine 5'-cyclic monophosphate (cGMP) in the regulation of the ionic slow channels in heart muscle is less well known than that of adenosine 3,'5'-cyclic monophosphate (cAMP). The effects of intracellular injection of cAMP and cGMP in cultured chick embryonic heart (ventricular) cells by the liposome method were studied. Injection of cAMP into the cells induced spontaneous slow action potentials that could be blocked by verapamil and nifedipine. Injection of cGMP blocked on-going slow action potentials, and this effect was reversed by increasing cAMP. Thus both cAMP and cGMP are involved in the regulation of the slow calcium channels in myocardial cells, and the two cyclic nucleotides are antagonistic.


1981 ◽  
Vol 97 (3) ◽  
pp. 405-411 ◽  
Author(s):  
Per Manhem ◽  
Lise Heding ◽  
Jörgen Malmquist ◽  
Bernt Hökfelt

Abstract. The effect of standing and physical exercise on catecholamines and cyclic nucleotides in plasma was measured in 8 patients with essential hypertension under standardized conditions before and after prolonged treatment with clonidine. Before clonidine medication noradrenaline, adrenaline and cyclic AMP (cAMP) increased in response to standing and bicycling for 20 min. No significant correlation was found between their absolute levels nor was the increase in cAMP following exercise correlated to the increase in noradrenaline. Standing and physical exercise were without effect on cyclic GMP (cGMP). Clonidine reduced the plasma noradrenaline concentration in supine position and the noradrenaline and the adrenaline response to standing and exercise. Plasma cAMP was uneffected by clonidine under basal conditions but the response to exercise was slightly reduced initially. During clonidine there was a positive correlation between the plasma levels of cAMP and noradrenaline following work. Clonidine produced an increase in plasma cGMP in supine position, immediately prior to bicycling and after 5 min of exercise.


1982 ◽  
Vol 94 (3) ◽  
pp. 1214-1217
Author(s):  
A. N. Koterov ◽  
A. V. Nikol'skii ◽  
E. F. Romantsev ◽  
L. A. Vernigorova

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