Muscarinic stimulation of submucosal glands in swine trachea

1988 ◽  
Vol 64 (1) ◽  
pp. 200-209 ◽  
Author(s):  
C. M. Yang ◽  
J. M. Farley ◽  
T. M. Dwyer
Keyword(s):  
Acetylcholine Receptors ◽  
Relative Proportion ◽  
Muscarinic Acetylcholine Receptors ◽  
Mucus Secretion ◽  
Submucosal Gland ◽  
Isolated Cells ◽  
Gland Cells ◽  
Submucosal Glands ◽  
Tracheal Explants

The properties of muscarinic acetylcholine receptors (mAChR) on tracheal explants and isolated submucosal gland cells were determined using [3H]quinuclidinyl benzilate ([3H]QNB) and N-[3H]methylscopolamine ([3H]NMS) as ligands. Analysis of competitive displacement of ([3H]NMS binding by pirenzepine demonstrated the presence of M1- (27 +/- 2%) and M2G- (73 +/- 2%) receptors on isolated tracheal submucosal gland cells (TSGC's) in control. Daily administration of diisopropylfluorophosphate (DFP) inhibited cholinesterase activity by greater than 95%. After 7 days of DFP treatment, [3H]QNB binding to intact TSGC's decreased from 14.2 +/- 0.6 to 6.3 +/- 0.8 fmol/10(6) cells; similarly, [3H]NMS binding fell from 8.1 +/- 1.9 to 2.0 +/- 0.8 fmol/10(6) cells. The loss of mAChR's was predominantly of the M2G subtype with the relative proportion dropping to 33%. In addition, 90% of the receptors assumed the high-affinity state for carbachol displacement of [3H]NMS. Mucus secretion was quantitated by measuring the release of 3H-labeled mucus macromolecules from explants of tracheal submucosal glands and isolated cells. Acetylcholine (ACh), 2 X 10(-5) M, stimulated mucus secretion by 2.5 and 2.3 times the basal rate, respectively. Elimination of acetylcholinesterase (AChe) by DFP increased the ACh sensitivity by 18- and 5-fold. Tracheal explants or TSGC's obtained 2 h after an in vivo DFP treatment showed a 6- and 3-fold ACh stimulation. This ACh sensitivity decreased during the continued daily dosing with DFP such that only a 1.3- and 1.1-fold ACh stimulation was apparent after 7 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential pial and penetrating arterial responses examined by optogenetic activation of astrocytes and neurons

2021 ◽  
pp. 0271678X2110103
Author(s):  
Nao Hatakeyama ◽  
Miyuki Unekawa ◽  
Juri Murata ◽  
Yutaka Tomita ◽  
Norihiro Suzuki ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Acetylcholine Receptors ◽  
Step Function ◽  
Muscarinic Acetylcholine Receptors ◽  
Cell Type ◽  
Function Type ◽  
Neuron Activation ◽  
Cell Type Specific ◽  
Arterial Responses

A variety of brain cells participates in neurovascular coupling by transmitting and modulating vasoactive signals. The present study aimed to probe cell type-dependent cerebrovascular (i.e., pial and penetrating arterial) responses with optogenetics in the cortex of anesthetized mice. Two lines of the transgenic mice expressing a step function type of light-gated cation channel (channelrhodopsine-2; ChR2) in either cortical neurons (muscarinic acetylcholine receptors) or astrocytes (Mlc1-positive) were used in the experiments. Photo-activation of ChR2-expressing astrocytes resulted in a widespread increase in cerebral blood flow (CBF), extending to the nonstimulated periphery. In contrast, photo-activation of ChR2-expressing neurons led to a relatively localized increase in CBF. The differences in the spatial extent of the CBF responses are potentially explained by differences in the involvement of the vascular compartments. In vivo imaging of the cerebrovascular responses revealed that ChR2-expressing astrocyte activation led to the dilation of both pial and penetrating arteries, whereas ChR2-expressing neuron activation predominantly caused dilation of the penetrating arterioles. Pharmacological studies showed that cell type-specific signaling mechanisms participate in the optogenetically induced cerebrovascular responses. In conclusion, pial and penetrating arterial vasodilation were differentially evoked by ChR2-expressing astrocytes and neurons.

scholarly journals Imaging Muscarinic Cholinergic Receptors in Human Brain in vivo with SPECT, [123I]4-Iododexetimide, and [123I]4-Iodolevetimide

1992 ◽  
Vol 12 (4) ◽  
pp. 562-570 ◽  
Author(s):  
Hans W. Müller-Gärtner ◽  
Alan A. Wilson ◽  
Robert F. Dannals ◽  
Henry N. Wagner ◽  
J. James Frost
Keyword(s):  
Human Brain ◽  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Acetylcholine Receptors ◽  
Brain Regions ◽  
Muscarinic Acetylcholine Receptors ◽  
Emission Computed Tomography ◽  
Nonspecific Binding ◽  
Muscarinic Acetylcholine

A method to image muscarinic acetylcholine receptors (muscarinic receptors) noninvasively in human brain in vivo was developed using [123I]4-iododexetimide ([123I]IDex), [123I]4-iodolevetimide ([123I]ILev), and single photon emission computed tomography (SPECT). [123I]IDex is a high-affinity muscarinic receptor antagonist. [123I]ILev is its pharmacologically inactive enantiomer and measures nonspecific binding of [123I]IDex in vitro. Regional brain activity after tracer injection was measured in four young normal volunteers for 24 h. Regional [123I]IDex and [123I]ILev activities were correlated early after injection, but not after 1.5 h. [123I]IDex activity increased over 7–12 h in neocortex, neostriatum, and thalamus, but decreased immediately after the injection peak in cerebellum. [123I]IDex activity was highest in neostriatum, followed in rank order by neocortex, thalamus, and cerebellum. [123I]IDex activity correlated with muscarinic receptor concentrations in matching brain regions. In contrast, [123I]ILev activity decreased immediately after the injection peak in all brain regions and did not correspond to muscarinic receptor concentrations. [123I]IDex activity in neocortex and neostriatum during equilibrium was six to seven times higher than [123I]ILev activity. The data demonstrate that [123I]IDex binds specifically to muscarinic receptors in vivo, whereas [123I]ILev represents the nonspecific part of [123I]IDex binding. Subtraction of [123I]ILev from [123I]IDex images on a pixel-by-pixel basis therefore reflects specific [123I]IDex binding to muscarinic receptors. Owing to its high specific binding, [123I]IDex has the potential to measure small changes in muscarinic receptor characteristics in vivo with SPECT. The use of stereoisomerism directly to measure nonspecific binding of [123I]IDex in vivo may reduce complexity in modeling approaches to muscarinic acetylcholine receptors in human brain.

Effect of anion transport inhibition on mucus secretion by airway submucosal glands

1997 ◽  
Vol 272 (2) ◽  
pp. L372-L377 ◽  
Author(s):  
S. K. Inglis ◽  
M. R. Corboz ◽  
A. E. Taylor ◽  
S. T. Ballard
Keyword(s):  
Cystic Fibrosis ◽  
Anion Transport ◽  
Mucus Secretion ◽  
Disulfonic Acid ◽  
Pathological Changes ◽  
Submucosal Gland ◽  
Anion Secretion ◽  
Submucosal Glands ◽  
Gland Duct

To model the airway glandular defect in cystic fibrosis (CF), the effect of anion secretion blockers on submucosal gland mucus secretion was investigated. Porcine distal bronchi were isolated, pretreated with a Cl- secretion blocker (bumetanide) and/or a combination of blockers to inhibit HCO3- secretion (dimethylamiloride, acetazolamide, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid), and then treated with acetylcholine (ACh), a glandular liquid and mucus secretagogue. Bronchi were then fixed, sectioned, and stained for mucins. Each gland duct was ranked for mucin content from zero (no mucin) to five (duct completely occluded with mucin). Untreated bronchi, bronchi treated only with ACh, and ACh-treated bronchi that received either bumetanide or the HCO3- secretion blockers all exhibited low gland duct mucin content (1.18 +/- 0.34, 0.59 +/- 0.07, 0.65 +/- 0.03, and 0.83 +/- 0.11, respectively). However, pretreatment with both Cl- and HCO3- secretion blockers before ACh addition resulted in substantial and significant ductal mucus accumulation (3.57 +/- 0.22). In situ videomicroscopy studies of intact airways confirmed these results. Thus inhibition of the anion (and presumably liquid) secretion response to ACh leads to mucus obstruction of submucosal gland ducts that resembles the early pathological changes observed in CF.

scholarly journals Presynaptic cholinergic neuromodulation alters the temporal dynamics of short-term depression at parvalbumin-positive basket cell synapses from juvenile CA1 mouse hippocampus

2015 ◽  
Vol 113 (7) ◽  
pp. 2408-2419 ◽  
Author(s):  
J. Josh Lawrence ◽  
Heikki Haario ◽  
Emily F. Stone
Keyword(s):  
Pyramidal Cell ◽  
Acetylcholine Receptors ◽  
Temporal Dynamics ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Calcium Transient ◽  
Muscarinic Acetylcholine Receptors ◽  
Presynaptic Calcium

Parvalbumin-positive basket cells (PV BCs) of the CA1 hippocampus are active participants in theta (5–12 Hz) and gamma (20–80 Hz) oscillations in vivo. When PV BCs are driven at these frequencies in vitro, inhibitory postsynaptic currents (IPSCs) in synaptically connected CA1 pyramidal cells exhibit paired-pulse depression (PPD) and multiple-pulse depression (MPD). Moreover, PV BCs express presynaptic muscarinic acetylcholine receptors (mAChRs) that may be activated by synaptically released acetylcholine during learning behaviors in vivo. Using acute hippocampal slices from the CA1 hippocampus of juvenile PV-GFP mice, we performed whole cell recordings from synaptically connected PV BC-CA1 pyramidal cell pairs to investigate how bath application of 10 μM muscarine impacts PPD and MPD at CA1 PV BC-pyramidal cell synapses. In accordance with previous studies, PPD and MPD magnitude increased with stimulation frequency. mAChR activation reduced IPSC amplitude and transiently reduced PPD, but MPD was largely maintained. Consistent with a reduction in release probability ( pr), MPD and mAChR activation increased both the coefficient of variation of IPSC amplitudes and the fraction of failures. Using variance-mean analysis, we converted MPD trains to pr functions and developed a kinetic model that optimally fit six distinct pr conditions. The model revealed that vesicular depletion caused MPD and that recovery from depression was dependent on calcium. mAChR activation reduced the presynaptic calcium transient fourfold and initial pr twofold, thereby reducing PPD. However, mAChR activation slowed calcium-dependent recovery from depression during sustained repetitive activity, thereby preserving MPD. Thus the activation of presynaptic mAChRs optimally protects PV BCs from vesicular depletion during short bursts of high-frequency activity.

Synthesis,18F-Labeling, and Biological Evaluation of Piperidyl and Pyrrolidyl Benzilates as in Vivo Ligands for Muscarinic Acetylcholine Receptors

2000 ◽  
Vol 43 (23) ◽  
pp. 4552-4562 ◽  
Author(s):  
Marc B. Skaddan ◽  
Michael R. Kilbourn ◽  
Scott E. Snyder ◽  
Phil S. Sherman ◽  
Tim J. Desmond ◽  
...  
Keyword(s):  
Acetylcholine Receptors ◽  
Biological Evaluation ◽  
Muscarinic Acetylcholine Receptors ◽  
Muscarinic Acetylcholine

Effect of epithelium on mucus secretion from feline tracheal submucosal glands

1989 ◽  
Vol 66 (2) ◽  
pp. 764-770 ◽  
Author(s):  
T. Sasaki ◽  
S. Shimura ◽  
H. Sasaki ◽  
T. Takishima
Keyword(s):  
Airway Epithelium ◽  
Inhibitory Action ◽  
Mucus Secretion ◽  
Submucosal Gland ◽  
Leukotriene D4 ◽  
Lipoxygenase Inhibitors ◽  
Beta Adrenergic Agonists ◽  
Submucosal Glands ◽  
Acid Metabolites ◽  
Mucosal Explants

We studied the effect of airway epithelium on mucus secretion by use of an isolated tracheal submucosal gland preparation reported previously (J. Appl. Physiol. 60: 1237–1247, 1986). Mucus glycoconjugate release from submucosal glands of feline trachea was examined using [3H]glucosamine as a mucus precursor. Isolated glands showed significantly higher secretory responses to cholinergic, alpha-, and beta-adrenergic agonists and dibutyryladenosine 3′,5′-cyclic monophosphate (average 400% of control) than the conventional tracheal mucosal explants, which contained epithelium and submucosal tissues in addition to submucosal glands (average 160% of control). The addition of isolated epithelium depressed the secretory response of isolated glands to the same level as that of tracheal explants. However, the supernatant from isolated epithelium failed to inhibit secretory responses to methacholine in isolated glands, suggesting that the epithelium-derived inhibitory factor to secretion may be short-lived. Leukotriene D4 antagonist (FPL 55712), cyclooxygenase and/or lipoxygenase inhibitors (indomethacin or BW 755C) caused no significant change in the inhibitory action of epithelium, suggesting that the inhibition is not due to arachidonic acid metabolites. The newly found secretory inhibitory action of epithelium is of particular interest in the pathogenesis of hypersecretion associated with epithelial damage.

Pirenzepine block of ACH-induced mucus secretion in tracheal submucosal gland cells

Life Sciences ◽  
1991 ◽  
Vol 48 (1) ◽  
pp. 59-67
Author(s):  
Jerry M. Farley ◽  
Terry M. Dwyer
Keyword(s):  
Mucus Secretion ◽  
Submucosal Gland ◽  
Gland Cells

Effects of Autoantibodies against M2 Muscarinic Acetylcholine Receptors on Rabbit Atria in vivo

Cardiology ◽  
2009 ◽  
Vol 112 (3) ◽  
pp. 180-187 ◽  
Author(s):  
Chang Ming Hong ◽  
Qiang Sun Zheng ◽  
Xiong Tao Liu ◽  
Fu Jun Shang ◽  
Hong Tao Wang ◽  
...  
Keyword(s):  
Acetylcholine Receptors ◽  
Muscarinic Acetylcholine Receptors ◽  
Muscarinic Acetylcholine ◽  
Rabbit Atria

scholarly journals Differences in Time Course of ACh and GABA Modulation of Excitatory Synaptic Potentials in Slices of Rat Hippocampus

2001 ◽  
Vol 86 (4) ◽  
pp. 1792-1802 ◽  
Author(s):  
Michael E. Hasselmo ◽  
Brian P. Fehlau
Keyword(s):  
Presynaptic Inhibition ◽  
Acetylcholine Receptors ◽  
Time Course ◽  
Onset Time ◽  
Afferent Input ◽  
Muscarinic Acetylcholine Receptors ◽  
Time Constants ◽  
Synaptic Potentials ◽  
Extracellular Potentials

Activation of muscarinic receptors and GABABreceptors causes presynaptic inhibition of glutamatergic synaptic potentials at excitatory feedback connections in cortical structures. These effects may regulate dynamics in cortical structures, with presynaptic inhibition allowing extrinsic afferent input to dominate during encoding, while the absence of presynaptic inhibition allows stronger excitatory feedback during retrieval or consolidation. However, proposals for a functional role of such modulatory effects strongly depend on the time course of these modulatory effects; how rapidly can they turn off and on? In brain slice preparations of hippocampal region CA1, we have explored the time course of suppression of extracellularly recorded synaptic potentials after pressure pulse application of acetylcholine and GABA. Acetylcholine causes suppression of extracellular potentials with onset time constants between 1 and 2 s, and decay constants ranging between 10 and 20 s, even with very brief injection pulses. GABA causes suppression of extracellular potentials with onset time constants between 0.2 and 0.7 s, and decay time constants that decrease to values shorter than 2 s for very brief injection pulses. These techniques do not give an exact measure of the physiological time course in vivo, but they give a notion of the relative time course of the two modulators. The slow changes due to activation of muscarinic acetylcholine receptors may alter the dynamics of cortical circuits over longer intervals (e.g., between different stages of waking and sleep), setting dynamics appropriate for encoding versus consolidation processes. The faster changes in synaptic potentials caused by GABA could cause changes within each cycle of the theta rhythm, rapidly switching between encoding and retrieval dynamics during exploration.

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