Evidence for age-associated reduction in acetylcholine release and smooth muscle response in the rat colon

1994 ◽  
Vol 267 (4) ◽  
pp. G515-G522 ◽  
Author(s):  
D. Roberts ◽  
D. Gelperin ◽  
J. W. Wiley
Keyword(s):  
Calcium Channels ◽  
Acetylcholine Release ◽  
Calcium Influx ◽  
Muscle Tension ◽  
Calcium Ionophore ◽  
Rat Colon ◽  
Neural Pathways ◽  
Dependent Manner ◽  
Ach Release ◽  
Age Dependent

The effect of aging was examined on cholinergically mediated contractions and acetylcholine (ACh) release in isolated colonic segments from Fischer (F344 x BN) F1 rats, 4-8 mo (postpubertal) and 22-28 mo (senescent) of age. This species demonstrates age-dependent slowing of colonic transit. Muscle tension response to electrical stimulation of cholinergic neural pathways and application of ACh was significantly decreased in preparations from senescent compared with postpubertal animals. We focused on the hypothesis that aging was associated with reduced ACh release that resulted from decreased calcium influx through membrane calcium channels. Aging did not affect either the synthesis of [3H]ACh from [3H]choline or the percentage of 3H released in the form of [3H]ACh. However, elevated KCl-evoked release of [3H]ACh was significantly reduced in tissue from senescent compared with postpubertal animals. Treatment with the calcium ionophore ionomycin increased [3H]ACh release in tissue from senescent animals to near postpubertal levels. However, increasing extracellular calcium concentration ([Ca2+]o) from 1.2 to 5 mM did not increase the amount of transmitter release in tissue from senescent animals to the levels observed with 1.2 mM [Ca2+]o in postpubertal tissue. The neuronal calcium channel antagonist omega-conotoxin GVIA inhibited acetylcholine release in a concentration-dependent manner with half-maximal inhibitory values of 1.8 and 8.2 nM for senescent and postpubertal preparations, respectively. In summary, age-dependent reduction in ACh release was observed in the rat colon myenteric plexus that may, in part, be associated with decreased calcium influx via membrane calcium channels.

scholarly journals Activation of TRPA1 by luminal stimuli induces EP4-mediated anion secretion in human and rat colon

2012 ◽  
Vol 302 (7) ◽  
pp. G690-G701 ◽  
Author(s):  
Izumi Kaji ◽  
Yukiko Yasuoka ◽  
Shin-ichiro Karaki ◽  
Atsukazu Kuwahara
Keyword(s):  
Host Defense ◽  
Transient Receptor Potential ◽  
Defense Mechanism ◽  
Ussing Chamber ◽  
Pcr Analysis ◽  
Rat Colon ◽  
Receptor Subtype ◽  
Neural Pathways ◽  
Dependent Manner ◽  
Anion Secretion

In gastrointestinal (GI) physiology, anion and fluid secretion is an important function for host defense and is induced by changes in the luminal environment. The transient receptor potential A1 (TRPA1) channel is considered to be a chemosensor in several sensory tissues. Although the function of TRPA1 has been studied in GI motility, its contribution to the transepithelial ion transport system has rarely been discussed. In the present study, we investigated the secretory effect of the potential TRPA1 agonist allyl isothiocyanate (AITC) in rat and human colon using an Ussing chamber. The mucosal application of AITC (10−6-10−3 M) induced Cl− and HCO3− secretion in a concentration-dependent manner, whereas the serosal application induced a significantly weaker effect. AITC-evoked anion secretion was attenuated by tissue pretreatment with piroxicam and prostaglandin (PG) E2; however, this secretion was not affected by TTX, atropine, or extracellular Ca2+ depletion. These experiments indicate that TRPA1 activation induces anion secretion through PG synthesis, independent of neural pathways in the colon. Further analysis also indicates that AITC-evoked anion secretion is mediated mainly by the EP4 receptor subtype. The magnitude of the secretory response exhibited segmental heterogeneity in rat colon. Real-time PCR analysis showed the segmental difference was corresponding to the differential expression of EP4 receptor and cyclooxygenase-1 and -2. In addition, RT-PCR, in situ hybridization, and immunohistochemical studies showed TRPA1 expression in the colonic epithelia. Therefore, we conclude that the activation of TRPA1 in colonic epithelial cells is likely involved in the host defense mechanism through rapid anion secretion.

scholarly journals Effects of enantiomers of β2-agonists on ACh release and smooth muscle contraction in the trachea

1998 ◽  
Vol 274 (1) ◽  
pp. L32-L38 ◽  
Author(s):  
Xiang-Yang Zhang ◽  
Feng-Xia Zhu ◽  
Michal A. Olszewski ◽  
N. Edward Robinson
Keyword(s):  
Smooth Muscle ◽  
High Performance ◽  
Muscle Tension ◽  
Electrical Field Stimulation ◽  
Smooth Muscle Contraction ◽  
Acute Administration ◽  
Dependent Manner ◽  
Ach Release ◽  
Concentration Dependent Manner ◽  
Parasympathetic Nerves

The β2-agonists currently used as bronchodilators are racemic mixtures of R- and S-enantiomers. In the present study, we examined the effects of enantiomers of the β2-agonists albuterol and formoterol on acetylcholine (ACh) release from equine trachealis parasympathetic nerves. ACh release was evoked by electrical field stimulation (20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography coupled with electrochemical detection. We also tested the effects of enantiomers of albuterol and formoterol on equine tracheal smooth muscle (TSM) contraction in response to exogenous ACh. R- and RS-albuterol (10−8 to 10−5 M) and RR- and RR/SS-formoterol (10−8 to 10−5 M) augmented ACh release in a concentration-dependent manner. Beginning at 10−6 M, SS-formoterol significantly increased ACh release, and at 10−5 M, release increased by 71.9 ± 8.7% over baseline. This effect was only observed, however, when the prejunctional muscarinic autoinhibitory effect of ACh was prevented with atropine. Both the RR- and SS-formoterol-induced increases in ACh release were abolished by the β2-antagonist ICI-118551 (3 × 10−7 M). The effect of S-albuterol on ACh release was variable, and the mean increase induced by 10−5 M was 30.8 ± 16.1% in the presence of atropine. In the muscle tension study, R- and RS-albuterol and RR- and RR/SS-formoterol (10−8 to 10−5 M) but not the S-enantiomers inhibited TSM contraction. Even though R-enantiomers augment ACh release, they potently inhibit TSM contraction. Because racemic β2-agonists are bronchodilators on acute administration, the postjunctional spasmolytic effects of R-enantiomers predominate over the spasmogenic effect evoked via increased ACh release. The S-enantiomers, in contrast, do not inhibit TSM contraction and therefore would not contribute to the observed bronchodilation of the racemate. The S-enantiomers do prejunctionally facilitate ACh release when prejunctional muscarinic autoreceptors are dysfunctional, suggesting a potentially deleterious effect.

Potentiation of acetylcholine release from tracheal parasympathetic nerves by cAMP

1996 ◽  
Vol 270 (4) ◽  
pp. L541-L546 ◽  
Author(s):  
X. Y. Zhang ◽  
N. E. Robinson ◽  
F. X. Zhu
Keyword(s):  
High Performance ◽  
Acetylcholine Release ◽  
Electrical Field Stimulation ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Ach Release ◽  
Electrical Field ◽  
Concentration Dependent Manner ◽  
Cyclic Monophosphate ◽  
Parasympathetic Nerves

We tested the hypothesis that increasing intracellular levels of adenosine 3', 5'-cyclic monophosphate (cAMP) increases acetylcholine (ACh) release from airway parasympathetic nerves. Muscle strips from equine trachea were preincubated for 60 min with 10(-7)M atropine, 10(-6)M neostigmine, and 10(-5) M guanethidine. The ACh release was evoked by electrical field stimulation (EFS, 20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography with electrochemical detection. Agents known to increase cAMP, i.e., forskolin (10(-6) - 10(-4) M), 8-bromoadenosine 3', 5'-cyclic monophosphate (8-BrcAMP; 10(-5)-10(-3) M), and 3-isobutyl-1-methylxanthine (IBMX ; 10(-5)-10(-3)M) was potentiated by IBMX but not mimicked by 1,9 dideoxyforskolin. To determine if the augmentation of Ach release facilitated EFS-induced ACh release in a concentration-dependent manner. Forskolin-induced augmentation of ACh release induced by activation of beta 2-adrenoceptors is mediated via cAMP-dependent pathways, we also examined the additive effects of 8-BrcAMP, forskolin, and IBMX with 10(-6)M isoproterenol (ISO), the concentration that maximally augments ACh release. Neither forskolin nor 8-BrcAMP potentiated the maximal augmentation produced by ISO, but inhibition of phosphodiesterase with IBMX (10(-4) and 10(-3)M) augmented the maximal effect of ISO. These observations indicate that neuronal cAMP is a physiological modulator of ACh release from airway parasympathetic nerves and mediates ISO-induced augmentation of ACh release. Bronchodilators that increase cAMP may therefore paradoxically augment ACh release while relaxing smooth muscle.

Maitotoxin stimulates hormonal release and calcium flux in rat anterior pituitary cells in vitro

1984 ◽  
Vol 247 (4) ◽  
pp. E520-E525
Author(s):  
G. Schettini ◽  
K. Koike ◽  
I. S. Login ◽  
A. M. Judd ◽  
M. J. Cronin ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Anterior Pituitary ◽  
Calcium Influx ◽  
Calcium Flux ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Anterior Pituitary Cells ◽  
Lh Release ◽  
Hormonal Release

The marine dinoflagellate toxin maitotoxin (MTX), an activator of calcium channels, stimulates the release of prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), and luteinizing hormone (LH) from monolayers of anterior pituitary cells in a dose-dependent manner. Maitotoxin significantly increased PRL, GH, and LH release within 1.5 min and TSH release within 3.5 min, and the stimulation continued for at least 1 h (P less than 0.01). MTX-stimulated hormonal release was blocked by the calcium channel blocker manganese (P less than 0.01). In freshly dispersed perifused pituitary cells in columns, exposure to MTX for 10 min markedly increased PRL, GH, TSH, and LH release for at least 1 h after withdrawal of the toxin. In other experiments, MTX significantly stimulated 45Ca2+ exchange by dispersed pituitary cells within 30 s, continuing for at least 30 min. We conclude that MTX increases anterior pituitary hormonal release, possibly by activating calcium channels, thereby increasing cellular calcium influx. Thus MTX may be a useful agent for investigating the involvement of Ca2+ in hormonal secretory processes.

Effect of calcium ionophore A23187 on pregnenolone metabolism to progesterone in rat granulosa cells

1988 ◽  
Vol 66 (7) ◽  
pp. 960-963 ◽  
Author(s):  
Benjamin K. Tsang ◽  
David F. Mattice ◽  
Ming Li ◽  
Elikplimi K. Asem
Keyword(s):  
Granulosa Cells ◽  
Calcium Influx ◽  
Calcium Ionophore ◽  
Acute Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Endogenous Substrate ◽  
Serum Gonadotropin

The effect of calcium ionophore A23187 on the metabolism of pregnenolone to progesterone was examined in rat granulosa cells during a 24-h culture period. Granulosa cells harvested from pregnant mare's serum gonadotropin treated immature rats were incubated in the presence and absence of the divalent cation ionophore A23187. The ionophore induced progesterone synthesis from both endogenous sterol substrate and exogenous pregnenolone in a time- and concentration-dependent manner. Pregnenolone metabolism was examined in the presence of aminoglutethimide phosphate, an inhibitor of endogenous pregnenolone production. Steroid secretion resulting from metabolism of endogenous substrate was more sensitive to A23187 in that a lower concentration of the ionophore was required to induce a significant increase than that noted for exogenous pregnenolone metabolism. In addition, progesterone production from endogenous sterol occurred 6 h earlier than the observed increase in the conversion of pregnenolone to progesterone. These results indicate that A23187 and therefore possibly enhanced calcium influx may play a significant role in the regulation of pregnenolone metabolism in granulosa cells depending on the duration of incubation. The earlier steroidogenic response from endogenous substrate may be a reflection of an acute effect of A23187 on certain steroidogenic steps proximal to pregnenolone production.

scholarly journals Phospholipid metabolism, calcium flux, and the receptor-mediated induction of chemotaxis in rabbit neutrophils.

1982 ◽  
Vol 93 (3) ◽  
pp. 690-697 ◽  
Author(s):  
D L Bareis ◽  
F Hirata ◽  
E Schiffmann ◽  
J Axelrod
Keyword(s):  
Arachidonic Acid ◽  
Calcium Influx ◽  
Calcium Ionophore ◽  
Receptor Activation ◽  
Calcium Flux ◽  
Ionophore A23187 ◽  
Dependent Manner ◽  
Arachidonic Acid Release ◽  
Chemotactic Peptide ◽  
Acid Release

Rabbit neutrophils were stimulated with the chemotactic peptide fMet-Leu-Phe in the presence of the methyltransferase inhibitors homocysteine (HCYS) and 3-deazaadenosine (3-DZA). HCYS and 3-DZA inhibited chemotaxis, phospholipid methylation, and protein carboxymethylation in a dose-dependent manner. The chemotactic peptide-stimulated release of [14C]arachidonic acid previously incorporated into phospholipid was also partially blocked by the methyltransferase inhibitors. Stimulation by fMet-Leu-Phe or the calcium ionophore A23187 caused release of arachidonic acid but not of previously incorporated [14C]-labeled linoleic, oleic, or stearic acids. Unlike the arachidonic acid release caused by fMet-Leu-Phe, release stimulated by the ionophore could not be inhibited by HCYS and 3-DZA, suggesting that the release was caused by a different mechanism or by stimulating a step after methylation in the pathway from receptor activation to arachidonic acid release. Extracellular calcium was required for arachidonic acid release, and methyltransferase inhibitors were found to partially inhibit chemotactic peptide-stimulated calcium influx. These results suggest that methylation pathways may be associated with the chemotactic peptide receptor stimulation of calcium influx and activation of a phospholipase A2 specific for cleaving arachidonic acid from phospholipids.

Platelet-activating factor and the kidney

1986 ◽  
Vol 251 (1) ◽  
pp. F1-F11 ◽  
Author(s):  
D. Schlondorff ◽  
R. Neuwirth
Keyword(s):  
De Novo ◽  
Mesangial Cells ◽  
Biological Activities ◽  
Platelet Activating Factor ◽  
Calcium Ionophore ◽  
Initial Step ◽  
Renal Physiology ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Isolated Kidney

Platelet-activating factor (PAF) represents a group of phospholipids with the basic structure of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine. A number of different cells are capable of producing PAF in response to various stimuli. The initial step of PAF formation is activation of phospholipase A2 in a calcium-dependent manner, yielding lyso-PAF. During this step arachidonic acid is also released and can be converted to its respective cyclooxygenase and lipoxygenase products. The lyso-PAF generated is then acetylated in position 2 of the glycerol backbone by a coenzyme A (CoA)-dependent acetyltransferase. An additional pathway may exist whereby PAF is generated de novo from 1-alkyl-2-acetyl-sn-glycerol by phosphocholine transferase. PAF inactivation in cells and blood is by specific acetylhydrolases. PAF exhibits a variety of biological activities including platelet and leukocyte aggregation and activation, increased vascular permeability, respiratory distress, decreased cardiac output, and hypotension. In the kidney PAF can produce decreases in blood flow, glomerular filtration, and fluid and electrolyte excretion. Intrarenal artery injection of PAF may also result in glomerular accumulation of platelets and leukocytes and mild proteinuria. PAF increases prostaglandin formation in the isolated kidney and in cultured glomerular mesangial cells. PAF also causes contraction of mesangial cells. Upon stimulation with calcium ionophore the isolated kidney, isolated glomeruli and medullary cells, and cultured mesangial cells are capable of producing PAF. The potential role for PAF in renal physiology and pathophysiology requires further investigation that may be complicated by 1) the multiple interactions of PAF, prostaglandins, and leukotrienes and 2) the autocoid nature of PAF, which may restrict its action to its site of generation.

Second-trimester maternal lipid profiles predict pregnancy complications in an age-dependent manner

2019 ◽  
Vol 299 (5) ◽  
pp. 1253-1260 ◽  
Author(s):  
Qi Wu ◽  
Lixia Zhang ◽  
Licong Huang ◽  
Yu Lei ◽  
Lin Chen ◽  
...  
Keyword(s):  
Pregnancy Complications ◽  
Lipid Profiles ◽  
Dependent Manner ◽  
Second Trimester ◽  
Age Dependent

scholarly journals Cloning and characterization of Ras-GRF2, a novel guanine nucleotide exchange factor for Ras.

1997 ◽  
Vol 17 (3) ◽  
pp. 1396-1406 ◽  
Author(s):  
N P Fam ◽  
W T Fan ◽  
Z Wang ◽  
L J Zhang ◽  
H Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Calcium Influx ◽  
Calcium Ionophore ◽  
Mitogen Activated Protein Kinase ◽  
Northern Analysis ◽  
Free Form ◽  
Guanine Nucleotide ◽  
Nucleotide Exchange ◽  
Iq Motif ◽  
Guanine Nucleotide Exchange

Conversion of Ras proteins into an activated GTP-bound state able to bind effector proteins is catalyzed by specific guanine nucleotide exchange factors in response to a large number of extracellular stimuli. Here we report the isolation of mouse cDNAs encoding Ras-GRF2, a multidomain 135-kDa protein containing a COOH-terminal Cdc25-related domain that stimulates release of GDP from Ras but not other GTPases in vitro. Ras-GRF2 bound specifically to immobilized Ras lacking bound nucleotides, suggesting stabilization of the nucleotide-free form of Ras as a mechanism of catalyzing nucleotide exchange. The NH2-terminal region of Ras-GRF2 is predicted to contain features common to various signaling proteins including two pleckstrin homology domains and a Dbl homology region. Ras-GRF2 also contains an IQ motif which was required for its apparent constitutive association with calmodulin in epithelial cells ectopically expressing Ras-GRF2. Transient expression of Ras-GRF2 in kidney epithelial cells stimulated GTP binding by Ras and potentiated calcium ionophore-induced activation of mitogen-activated protein kinase (ERK1) dependent upon the IQ motif. Calcium influx caused Ras-GRF2 subcellular localization to change from cytosolic to peripheral, suggesting a possible mechanism for controlling Ras-GRF2 interactions with Ras at the plasma membrane. Epithelial cells overexpressing Ras-GRF2 are morphologically transformed and grow in a disorganized manner with minimal intercellular contacts. Northern analysis indicated a 9-kb GRF2 transcript in brain and lung, where p135 Ras-GRF2 is known to be expressed, and RNAs of 12 kb and 2.2 kb were detected in several tissues. Thus, Ras-GRF2 proteins with different domain structures may be widely expressed and couple diverse extracellular signals to Ras activation.

Deletion of murine tau gene increases tau aggregation in a human mutant tau transgenic mouse model

2010 ◽  
Vol 38 (4) ◽  
pp. 1001-1005 ◽  
Author(s):  
Kunie Ando ◽  
Karelle Leroy ◽  
Céline Heraud ◽  
Anna Kabova ◽  
Zehra Yilmaz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Double Mutant ◽  
Transgenic Mouse Model ◽  
Tau Proteins ◽  
Dependent Manner ◽  
Age Dependent ◽  
Ad Alzheimer’S Disease ◽  
Tau Aggregation ◽  
The Brain

We have reported previously a tau transgenic mouse model (Tg30tau) overexpressing human 4R1N double-mutant tau (P301S and G272V) and that develops AD (Alzheimer's disease)-like NFTs (neurofibrillary tangles) in an age-dependent manner. Since murine tau might interfere with the toxic effects of human mutant tau, we set out to analyse the phenotype of our Tg30tau model in the absence of endogenous murine tau with the aim to reproduce more faithfully a model of human tauopathy. By crossing the Tg30tau line with TauKO (tau-knockout) mice, we have obtained a new mouse line called Tg30×TauKO that expresses only exogenous human double-mutant 4R1N tau. Whereas Tg30×TauKO mice express fewer tau proteins compared with Tg30tau, they exhibit augmented sarkosyl-insoluble tau in the brain and an increased number of Gallyas-positive NFTs in the hippocampus. Taken together, exclusion of murine tau causes accelerated tau aggregation during aging of this mutant tau transgenic model.

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