Inhibitory action of SKPYMRFamide on acetylcholine receptors of helix aspersa neurons: Role of second messengers

A possible role of 5α-androstane-3α,17β-diol (3α-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3α-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 μg/100 g body wt) between 13 and 30 days of age; at 33–35 days of age only the 300 μg dose caused some inhibition of FSH release. Results were more complex if 3α-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3α-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3α-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3α-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3α-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3α-androstanediol on FSH secretion is limited in the presence of oestradiol.

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Nitric oxide inhibits neuronal nitric oxide synthase by interacting with the heme prosthetic group. Role of tetrahydrobiopterin in modulating the inhibitory action of nitric oxide.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)31854-9 ◽

1994 ◽

Vol 269 (34) ◽

pp. 21644-21649 ◽

Cited By ~ 2

Author(s):

J.M. Griscavage ◽

J.M. Fukuto ◽

Y. Komori ◽

L.J. Ignarro

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Inhibitory Action ◽

Neuronal Nitric Oxide Synthase ◽

Prosthetic Group ◽

Heme Prosthetic Group ◽

Oxide Synthase

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Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABAA and Nicotinic Acetylcholine Receptors

Toxins ◽

10.3390/toxins13020164 ◽

2021 ◽

Vol 13 (2) ◽

pp. 164

Author(s):

Lina Son ◽

Elena Kryukova ◽

Rustam Ziganshin ◽

Tatyana Andreeva ◽

Denis Kudryavtsev ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Gabaa Receptors ◽

Binding Sites ◽

Acetylcholine Receptors ◽

Nicotinic Acetylcholine ◽

High Affinity ◽

Central Loop ◽

Acetylcholine Binding Proteins ◽

Α7 Nachrs

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.

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Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior

Molecular Psychiatry ◽

10.1038/s41380-021-01016-1 ◽

2021 ◽

Author(s):

Young-Min Han ◽

Min Sun Kim ◽

Juyeong Jo ◽

Daiha Shin ◽

Seung-Hae Kwon ◽

...

Keyword(s):

Inhibitory Action ◽

Time Course ◽

Molecular Mechanisms ◽

Late Phase ◽

Fine Tuning ◽

Dependent Manner ◽

Middle Phase ◽

Temporal Shift

AbstractThe fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.

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Ca2+ Microdomains, Calcineurin and the Regulation of Gene Transcription

Cells ◽

10.3390/cells10040875 ◽

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.

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Role of second messengers in cholesterol efflux

Atherosclerosis ◽

10.1016/0021-9150(94)93712-5 ◽

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

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Rapid kinetics of second messenger production in bitter taste

AJP Cell Physiology ◽

10.1152/ajpcell.1996.270.3.c926 ◽

1996 ◽

Vol 270 (3) ◽

pp. C926-C931 ◽

Cited By ~ 56

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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