scholarly journals Novel Role of Brain Stem Pedunculopontine Tegmental Adenylyl Cyclase in the Regulation of Spontaneous REM Sleep in the Freely Moving Rat

2005 ◽  
Vol 94 (3) ◽  
pp. 1928-1937 ◽  
Author(s):  
Subimal Datta ◽  
Sarah L. Prutzman
Keyword(s):  
Adenylyl Cyclase ◽  
Signaling Pathway ◽  
Rem Sleep ◽  
Slow Wave Sleep ◽  
Kainate Receptors ◽  
Camp Signaling ◽  
Dependent Manner ◽  
Camp Signaling Pathway ◽  
Freely Moving ◽  
Different Doses

Physiological activation of kainate receptors and GABAB receptors within the pedunculopontine tegmentum (PPT) is involved in regulation of rapid-eye-movement (REM) sleep. Because these two types of receptors may also directly and/or indirectly activate the intracellular cyclic adenosine monophosphate (cAMP) signaling pathway, we hypothesized that this signaling pathway may be involved in the PPT to regulate spontaneous REM sleep. To test this hypothesis, four different doses (0.25, 0.50, 0.75, and 1.0 nmol) of a specific adenylyl cyclase (AC) inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536), were microinjected bilaterally (100 nl/site) into the PPT, and the effects on REM sleep in freely moving chronically instrumented rats were quantified. By comparing alterations in the patterns of REM sleep after control injections of vehicle or one of the four different doses of SQ22536, the contributions made by each dose of SQ22536 to REM sleep were evaluated. The results demonstrated that the local microinjection of AC inhibitor SQ22536 into the PPT decreased the total amount of REM sleep for 3 h and increased slow-wave sleep (SWS) for 2 h in a dose-dependent manner. This reduction in REM sleep was due to increased latency and decreased frequency of REM sleep episodes. These results provide evidence that inhibition of AC within the PPT can successfully reduce REM sleep. These findings suggest that activation of the cAMP-signaling pathway within the cholinergic cell compartment of the PPT is an intracellular biochemical/molecular step for generating REM sleep in the freely moving rat.

scholarly journals Assessment of cellular mechanisms contributing to cAMP compartmentalization in pulmonary microvascular endothelial cells

2012 ◽  
Vol 302 (6) ◽  
pp. C839-C852 ◽  
Author(s):  
Wei P. Feinstein ◽  
Bing Zhu ◽  
Silas J. Leavesley ◽  
Sarah L. Sayner ◽  
Thomas C. Rich
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Microvascular Endothelial Cells ◽  
Camp Production ◽  
Barrier Integrity ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Camp Signaling Pathway ◽  
Microvascular Endothelial

Cyclic AMP signals encode information required to differentially regulate a wide variety of cellular responses; yet it is not well understood how information is encrypted within these signals. An emerging concept is that compartmentalization underlies specificity within the cAMP signaling pathway. This concept is based on a series of observations indicating that cAMP levels are distinct in different regions of the cell. One such observation is that cAMP production at the plasma membrane increases pulmonary microvascular endothelial barrier integrity, whereas cAMP production in the cytosol disrupts barrier integrity. To better understand how cAMP signals might be compartmentalized, we have developed mathematical models in which cellular geometry as well as total adenylyl cyclase and phosphodiesterase activities were constrained to approximate values measured in pulmonary microvascular endothelial cells. These simulations suggest that the subcellular localizations of adenylyl cyclase and phosphodiesterase activities are by themselves insufficient to generate physiologically relevant cAMP gradients. Thus, the assembly of adenylyl cyclase, phosphodiesterase, and protein kinase A onto protein scaffolds is by itself unlikely to ensure signal specificity. Rather, our simulations suggest that reductions in the effective cAMP diffusion coefficient may facilitate the formation of substantial cAMP gradients. We conclude that reductions in the effective rate of cAMP diffusion due to buffers, structural impediments, and local changes in viscosity greatly facilitate the ability of signaling complexes to impart specificity within the cAMP signaling pathway.

Microinjection of glutamate into the pedunculopontine tegmentum induces REM sleep and wakefulness in the rat

2001 ◽  
Vol 280 (3) ◽  
pp. R752-R759 ◽  
Author(s):  
Subimal Datta ◽  
Eric E. Spoley ◽  
Elissa H. Patterson
Keyword(s):  
Rem Sleep ◽  
Slow Wave Sleep ◽  
Excitatory Amino Acid ◽  
Optimal Dose ◽  
Saline Control ◽  
Second Messenger Systems ◽  
Freely Moving ◽  
Polygraphic Recording ◽  
The Brain ◽  
Different Doses

The aim of this study was to test the hypothesis that the cells in the brain stem pedunculopontine tegmentum (PPT) are critically involved in the normal regulation of wakefulness and rapid eye movement (REM) sleep. To test this hypothesis, one of four different doses of the excitatory amino acid l-glutamate (15, 30, 60, and 90 ng) or saline (control vehicle) was microinjected unilaterally into the PPT while the effects on wakefulness and sleep were quantified in freely moving chronically instrumented rats. All microinjections were made during wakefulness and were followed by 6 h of polygraphic recording. Microinjection of 15- ng (0.08 nmol) and 30-ng (0.16 nmol) doses ofl-glutamate into the PPT increased the total amount of REM sleep. Both doses of l-glutamate increased REM sleep at the expense of slow-wave sleep (SWS) but not wakefulness. Interestingly, the 60-ng (0.32 nmol) dose of l-glutamate increased both REM sleep and wakefulness. The total increase in REM sleep after the 60-ng dose of l-glutamate was significantly less than the increase from the 30-ng dose. The 90-ng (0.48 nmol) dose ofl-glutamate kept animals awake for 2–3 h by eliminating both SWS and REM sleep. These results show that thel-glutamate microinjection into the PPT can increase wakefulness and/or REM sleep depending on the dosage. These findings support the hypothesis that excitation of the PPT cells is causal to the generation of wakefulness and REM sleep in the rat. In addition, the results of this study led to the identification of the PPT dosage of l-glutamate that optimally induces wakefulness and REM sleep. The knowledge of this optimal dose will be useful in future studies investigating the second messenger systems involved in the regulation of wakefulness and REM sleep.

scholarly journals Role of cAMP in Double Switch of Glucagon Secretion

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 896
Author(s):  
Jan Zmazek ◽  
Vladimir Grubelnik ◽  
Rene Markovič ◽  
Marko Marhl
Keyword(s):  
Glucose Metabolism ◽  
Signaling Pathway ◽  
Cell Model ◽  
Dominant Role ◽  
Glucagon Secretion ◽  
Camp Signaling ◽  
Independent Manner ◽  
Metabolic Switch ◽  
Camp Signaling Pathway ◽  
Double Switch

Glucose metabolism plays a crucial role in modulating glucagon secretion in pancreatic alpha cells. However, the downstream effects of glucose metabolism and the activated signaling pathways influencing glucagon granule exocytosis are still obscure. We developed a computational alpha cell model, implementing metabolic pathways of glucose and free fatty acids (FFA) catabolism and an intrinsically activated cAMP signaling pathway. According to the model predictions, increased catabolic activity is able to suppress the cAMP signaling pathway, reducing exocytosis in a Ca2+-dependent and Ca2+ independent manner. The effect is synergistic to the pathway involving ATP-dependent closure of KATP channels and consequent reduction of Ca2+. We analyze the contribution of each pathway to glucagon secretion and show that both play decisive roles, providing a kind of “secure double switch”. The cAMP-driven signaling switch plays a dominant role, while the ATP-driven metabolic switch is less favored. The ratio is approximately 60:40, according to the most recent experimental evidence.

scholarly journals Increased Rho-kinase-mediated prostate contractions associated with impairment of β-adrenergic-cAMP-signaling pathway by chronic nitric oxide deficiency

2015 ◽  
Vol 758 ◽  
pp. 24-30 ◽  
Author(s):  
Fabiano Beraldi Calmasini ◽  
Luiz Osório Silveira Leiria ◽  
Marcos José Alves ◽  
Fernando Ricardo Báu ◽  
Eduardo Costa Alexandre ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Rho Kinase ◽  
Camp Signaling ◽  
Camp Signaling Pathway ◽  
Nitric Oxide Deficiency

ChemInform Abstract: Ansellone A (I), a Sesterterpenoid Isolated from the Nudibranch Cadlina luteromarginata and the Sponge Phorbas sp., Activates the cAMP Signaling Pathway.

ChemInform ◽  
2010 ◽  
Vol 41 (48) ◽  
pp. no-no
Author(s):  
Julie Daoust ◽  
Angelo Fontana ◽  
Catherine E. Merchant ◽  
Nicole J. de Voogd ◽  
Brian O. Patrick ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Camp Signaling ◽  
Camp Signaling Pathway

Neostriatal administration of somatostatin: differential effect of small and large doses on behavior and motor control

1977 ◽  
Vol 55 (2) ◽  
pp. 234-242 ◽  
Author(s):  
M. Rezek ◽  
V. Havlicek ◽  
L. Leybin ◽  
C. Pinsky ◽  
E. A. Kroeger ◽  
...  
Keyword(s):  
Motor Control ◽  
Eye Movements ◽  
Slow Wave ◽  
Rem Sleep ◽  
Differential Effect ◽  
Slow Wave Sleep ◽  
Small Doses ◽  
Freely Moving ◽  
Behavioral Excitation ◽  
Higher Doses

The administration of small doses of somatostatin (SRIF) (0.01 and 0.1 μg) into the neostriatal complex of unrestrained, freely moving rats induced general behavioral excitation associated with a variety of stereotyped movements, tremors, and a reduction of rapid eye movements (REM) and deep slow wave sleep (SWS). In contrast, the higher doses of SRIF (1.0 and 10.0 μg) caused movements to be uncoordinated and frequently induced more severe difficulties in motor control such as contralateral hemiplegia-in-extension which restricted or completely prevented the expression of normal behavioral patterns. As a result, the animals appeared drowsy and inhibited. Analysis of the sleep-waking cycle revealed prolonged periods of a shallow SWS while REM sleep and deep SWS were markedly reduced; electroencephalogram recordings revealed periods of dissociation from behavior. The administration of endocrinologically inactive as well as the active analogues of SRIF failed to induce effects comparable with those observed after the administration of the same dose of the native hormone (10.0 μg).

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