Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels

1998 ◽  
Vol 78 (1) ◽  
pp. 53-97 ◽  
Author(s):  
FRANK M. FARACI ◽  
DONALD D. HEISTAD
Keyword(s):  
Potassium Channels ◽  
Cerebral Circulation ◽  
Second Messengers ◽  
Chronic Hypertension ◽  
Major Mechanism ◽  
Disease States ◽  
Vasoactive Factors ◽  
New Concepts ◽  
Intracellular Second Messengers

Faraci, Frank M., and Donald D. Heistad. Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels. Physiol. Rev. 78: 53–97, 1998. — Several new concepts have emerged in relation to mechanisms that contribute to regulation of the cerebral circulation. This review focuses on some physiological mechanisms of cerebral vasodilatation and alteration of these mechanisms by disease states. One mechanism involves release of vasoactive factors by the endothelium that affect underlying vascular muscle. These factors include endothelium-derived relaxing factor (nitric oxide), prostacyclin, and endothelium-derived hyperpolarizing factor(s). The normal vasodilator influence of endothelium is impaired by some disease states. Under pathophysiological conditions, endothelium may produce potent contracting factors such as endothelin. Another major mechanism of regulation of cerebral vascular tone relates to potassium channels. Activation of potassium channels appears to mediate relaxation of cerebral vessels to diverse stimuli including receptor-mediated agonists, intracellular second messengers, and hypoxia. Endothelial- and potassium channel-based mechanisms are related because several endothelium-derived factors produce relaxation by activation of potassium channels. The influence of potassium channels may be altered by disease states including chronic hypertension, subarachnoid hemorrhage, and diabetes.

Regulation of annexin I in adipogenesis: cAMP-independent action of methylisobutylxanthine

1992 ◽  
Vol 262 (1) ◽  
pp. C91-C97 ◽  
Author(s):  
W. T. Wong ◽  
H. S. Nick ◽  
S. C. Frost
Keyword(s):  
Adrenergic Receptor ◽  
Cellular Differentiation ◽  
Culture Medium ◽  
Potential Role ◽  
De Novo ◽  
Second Messengers ◽  
Annexin I ◽  
Intracellular Second Messengers ◽  
Camp And Cgmp

The differentiation of 3T3-L1 fibroblasts to adipocytes can be accelerated by the addition of 1-methyl-3-isobutylxanthine (MIX), insulin, and dexamethasone to the culture medium. During differentiation, we have demonstrated that the level of both annexin I mRNA and protein decreases. The half-times for this reduction were 2 h and 10 h for annexin I mRNA and protein, respectively. Of the added agents in the differentiation medium, only MIX caused a decline in annexin I expression in 3T3-L1 fibroblasts. The MIX effect in fibroblasts was reversible and required de novo transcription but not protein synthesis. Although MIX could be replaced by high levels of theophylline, neither agonists of the beta-adrenergic receptor nor intracellular second messengers, cAMP and cGMP, were able to reduce annexin I. The potential role of annexin I in cellular differentiation is discussed.

scholarly journals Cerebral circulation: humoral regulation and effects of chronic hypertension.

1990 ◽  
Vol 1 (1) ◽  
pp. 53-57
Author(s):  
F M Faraci ◽  
G L Baumbach ◽  
D D Heistad
Keyword(s):  
Blood Flow ◽  
Choroid Plexus ◽  
Blood Vessels ◽  
Cerebral Circulation ◽  
Systemic Blood Pressure ◽  
Chronic Hypertension ◽  
Cerebral Blood Vessels ◽  
New Concepts ◽  
Cerebral Arterioles ◽  
Relationship Of

New concepts have emerged in recent years concerning regulation of cerebral circulation. The purpose of this review is to summarize briefly several of these concepts. First, humoral mechanisms may have important effects on cerebral blood vessels and blood flow to choroid plexus. Recent evidence suggests that several vasoactive peptides may have major effects on fluid and ion balance in the brain by altering blood flow to the choroid plexus and possibly the production of cerebrospinal fluid. Second, chronic hypertension produces structural remodeling and hypertrophy of cerebral blood vessels and a shift in the relationship of cerebral blood flow to systemic blood pressure. Third, endothelium-dependent responses of cerebral arterioles to receptor and nonreceptor mediated agonists are impaired during chronic hypertension. Alterations in endothelium-dependent responses of cerebral arterioles during chronic hypertension appears to be due to release of an endothelium-derived contracting factor.

scholarly journals Ca2+ Microdomains, Calcineurin and the Regulation of Gene Transcription

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Gerald Thiel ◽  
Tobias Schmidt ◽  
Oliver G. Rössler
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Gene Transcription ◽  
Intracellular Signaling ◽  
Second Messengers ◽  
Major Function ◽  
Surface Receptors ◽  
Dependent Protein

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression.

scholarly journals Macrocyclic Peptides as Allosteric Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

2021 ◽  
Author(s):  
Matthijs van Haren ◽  
Yurui Zhang ◽  
Vito Thijssen ◽  
Ned Buijs ◽  
Yongzhi Gao ◽  
...  
Keyword(s):  
Allosteric Inhibitors ◽  
Methyl Donor ◽  
Disease States ◽  
Macrocyclic Peptides

Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide to form 1-methylnicotinamide (MNA) using S-adenosyl-L-methionine (SAM) as the methyl donor. The complexity of the role of NNMT in healthy and disease states is slowly...

Role of second messengers in cholesterol efflux

1994 ◽  
Vol 109 (1-2) ◽  
pp. 177
Author(s):  
E.L. Bierman ◽  
M. Deeg ◽  
A. Mendez ◽  
S. Garver ◽  
B. Hokland ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Second Messengers

Rapid kinetics of second messenger production in bitter taste

1996 ◽  
Vol 270 (3) ◽  
pp. C926-C931 ◽  
Author(s):  
A. I. Spielman ◽  
H. Nagai ◽  
G. Sunavala ◽  
M. Dasso ◽  
H. Breer ◽  
...  
Keyword(s):  
Bitter Taste ◽  
Second Messengers ◽  
Second Messenger ◽  
Mouse Strains ◽  
Protective Mechanism ◽  
Transient Nature ◽  
Sucrose Octaacetate ◽  
Rapid Kinetics ◽  
First Time

The tasting of bitter compounds may have evolved as a protective mechanism against ingestion of potentially harmful substances. We have identified second messengers involved in bitter taste and show here for the first time that they are rapid and transient. Using a quench-flow system, we have studied bitter taste signal transduction in a pair of mouse strains that differ in their ability to taste the bitter stimulus sucrose octaacetate (SOA); however, both strains taste the bitter agent denatonium. In both strains of mice, denatonium (10 mM) induced a transient and rapid increase in levels of the second messenger inositol 1,4,5-trisphosphate (IP3) with a maximal production near 75-100 ms after stimulation. In contrast, SOA (100 microM) brought about a similar increase in IP3 only in SOA-taster mice. The response to SOA was potentiated in the presence of GTP (1 microM). The GTP-enhanced SOA-response supports a G protein-mediated response for this bitter compound. The rapid kinetics, transient nature, and specificity of the bitter taste stimulus-induced IP3 formation are consistent with the role of IP3 as a second messenger in the chemoelectrical transduction of bitter taste.

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