Carbenoxolone reduces cyclic nucleotides level, destabilizes maturation promoting factor and induces meiotic exit from diplotene arrest in rat cumulus oocytes complexes cultured in vitro

Hormonal regulation of intestinal cholesterol synthesis was studied both in vitro and in vivo. Cholesterol synthesis rate was determined by measurement of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.34) activity and by incorporation [14C]acetate into sterol. In vitro studies utilized organ culture of canine ileal mucosa. During 6-h culture, reductase activity was stimulated sevenfold. Insulin (10-6 M) augmented this rise to 144 +/- 7% of th control activity, while 10(-8) M glucagon, 10(-3) M adenosine 3',5'-cyclic monophosphate, and 3-isobutyl-1-methylxanthine suppressed activity (final reductase activity was 83 +/- 3%, 75 +/- 4%, and 41 +/- 3%, respectively, of cultured control values). In vivo studies utilized dogs with isolated Thiry-Vella ileal fistulas. In vivo, insulin doubled reductase activity while glucagon led to a 42 +/- 9% suppression. It is concluded that insulin and glucagon may be potential physiological regulators of intestinal cholesterol synthesis. The glucagon effect may be mediated by cyclic nucleotides.

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Oocyte maturation and quality: role of cyclic nucleotides

Reproduction ◽

10.1530/rep-15-0606 ◽

2016 ◽

Vol 152 (5) ◽

pp. R143-R157 ◽

Cited By ~ 64

Author(s):

R B Gilchrist ◽

A M Luciano ◽

D Richani ◽

H T Zeng ◽

X Wang ◽

...

Keyword(s):

Cyclic Nucleotides ◽

Treatment Options ◽

Oocyte Quality ◽

Fertility Treatment ◽

Lower Efficiency ◽

Oocyte Meiosis ◽

Developmental Capacity ◽

Oocyte Meiotic Maturation

The cyclic nucleotides, cAMP and cGMP, are the key molecules controlling mammalian oocyte meiosis. Their roles in oocyte biology have been at the forefront of oocyte research for decades, and many of the long-standing controversies in relation to the regulation of oocyte meiotic maturation are now resolved. It is now clear that the follicle prevents meiotic resumption through the actions of natriuretic peptides and cGMP – inhibiting the hydrolysis of intra-oocyte cAMP – and that the pre-ovulatory gonadotrophin surge reverses these processes. The gonadotrophin surge also leads to a transient spike in cAMP in the somatic compartment of the follicle. Research over the past two decades has conclusively demonstrated that this surge in cAMP is important for the subsequent developmental capacity of the oocyte. This is important, as oocyte in vitro maturation (IVM) systems practised clinically do not recapitulate this cAMP surge in vitro, possibly accounting for the lower efficiency of IVM compared with clinical IVF. This review particularly focuses on this latter aspect – the role of cAMP/cGMP in the regulation of oocyte quality. We conclude that clinical practice of IVM should reflect this new understanding of the role of cyclic nucleotides, thereby creating a new generation of ART and fertility treatment options.

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CGRP and ANF cause relaxation of opossum internal anal sphincter via different mechanisms

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1991.260.5.g764 ◽

1991 ◽

Vol 260 (5) ◽

pp. G764-G769 ◽

Cited By ~ 4

Author(s):

S. Rattan ◽

C. Moummi ◽

S. Chakder

Keyword(s):

Smooth Muscle ◽

Anal Sphincter ◽

Cyclic Nucleotides ◽

Internal Anal Sphincter ◽

Camp Content ◽

Calcitonin Gene ◽

Before And After ◽

Camp And Cgmp

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.

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Activity of Maturation Promoting Factor (MPF) and distribution of mitochondria in murine in vivo and in vitro matured oocytes with different culture media from IVM

Fertility and Sterility ◽

10.1016/s0015-0282(03)01675-3 ◽

2003 ◽

Vol 80 ◽

pp. 267

Author(s):

Hiroaki Yoshida ◽

Nobuya Aono ◽

Tomoyuki Yoshida ◽

Takuya Wakai ◽

Hiroshi Sasada ◽

...

Keyword(s):

Culture Media ◽

Maturation Promoting Factor

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In Vitro Studies of the Testis: The Effect of LH on Cyclic Nucleotides

Hormone and Metabolic Research ◽

10.1055/s-0028-1092783 ◽

1979 ◽

Vol 11 (10) ◽

pp. 573-577 ◽

Cited By ~ 2

Author(s):

T. Lin ◽

J. Marchwinski ◽

H. Nankin

Keyword(s):

Cyclic Nucleotides ◽

In Vitro Studies

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Sodium regulation of GAF domain function

Biochemical Society Transactions ◽

10.1042/bst0351032 ◽

2007 ◽

Vol 35 (5) ◽

pp. 1032-1034 ◽

Cited By ~ 13

Author(s):

M.J. Cann

Keyword(s):

Cyclic Nucleotides ◽

Protein Domain ◽

Genetic Ablation ◽

Anabaena Pcc 7120 ◽

Cyanobacterium Anabaena ◽

Signal Changes ◽

Sodium Regulation ◽

Pcc 7120 ◽

Camp And Cgmp

Cyclic nucleotide PDEs (phosphodiesterases) regulate cellular levels of cAMP and cGMP by controlling the rate of degradation. Several mammalian PDE isoforms possess N-terminal GAF (found in cGMP PDEs, Anabaena adenylate cyclases and Escherichia coli FhlA; where FhlA is formate hydrogen lyase transcriptional activator) domains that bind cyclic nucleotides. Similarly, the CyaB1 and CyaB2 ACs (adenylate cyclases) of the cyanobacterium Anabaena PCC 7120 bind cAMP through one (CyaB1) or two (CyaB2) N-terminal GAF domains and mediate autoregulation of the AC domain. Sodium inhibits the activity of CyaB1, CyaB2 and mammalian PDE2A in vitro through modulation of GAF domain function. Furthermore, genetic ablation of cyaB1 and cyaB2 gives rise to Anabaena strains defective in homoeostasis at limiting sodium. Sodium regulation of GAF domain function has therefore been conserved since the eukaryotic/prokaryotic divergence. The GAF domain is the first identified protein domain to directly sense and signal changes in environmental sodium.

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The generation and regulation of lymphocyte populations: evidence from differentiative induction systems in vitro.

Journal of Experimental Medicine ◽

10.1084/jem.147.6.1727 ◽

1978 ◽

Vol 147 (6) ◽

pp. 1727-1743 ◽

Cited By ~ 116

Author(s):

M P Scheid ◽

G Goldstein ◽

E A Boyse

Keyword(s):

B Cells ◽

Cyclic Nucleotides ◽

General Scheme ◽

Pharmacological Agents ◽

Inductive Effects ◽

Camp Induction ◽

Camp And Cgmp ◽

Lymphocyte Populations ◽

Two Populations

Results with a dual assay, for the induction of Thy-1+ T cells and of CR+ B cells from marker-negative precursors, confirm that thymopoietin is at present the only known selective inducer of prothymocytes. In contrast, various inducers, including ubiquitin, are active in both assays. Pharmacological evidence indicates that there are different cellular receptors for ubiquitin and thymopoietin. Prothymocytes and pro-CR+ B cells compose two distinct populations in bone marrow and spleen; their distribution in density gradients is different, and elimination of either population enriches the other proportionately. There are no noteworthy differences between induction of these two populations in regard to (a) kinetics, (b) dependence on temperature and protein synthesis, (c) activation by cAMP, and (d) inhibition by cGMP. The opposite inductive effects of cAMP and cGMP were corroborated by the use of pharmacological agents that raise or lower the levels of intracellular cyclic nucleotides. In contrast, a third induction assay, which monitors acquisition of the PC+ surface phenotype, indicates that this differentiative step, the last known for B cells, is initiated by cGMP and inhibited by cAMP. Induction of PC is also inhibited by thymopoietin, signifying that the inductive selectivity of thymopoietin is not due to restriction of its receptors to the T lineage cells. Rather it seems that receptors for thymopoietin occur also on PC-inducible and other B cells, although in this case geared biochemically to inhibition rather than expression of the succeeding gene program. This suggests a role for thymopoietin in the coordinated interregulation of lymphocyte classes, in addition to its better-known function as the thymic inducer of prothymocytes. Present data conform to a general scheme in which the cyclic nucleotides cAMP and cGMP, and agents that affect intracellular levels of these mediators, influence reciprocally the early and late (functional) phases of lymphocyte differentiation as a whole, while thymopoietin influences reciprocally the differentiation of the B and T classes of lymphocyte.

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