Use Of Acetylcholine Research Articles

Skewing information flow through pre- and postsynaptic plasticity in the mushroom bodies of Drosophila.

Animal brains need to store information to construct a representation of their environment. Knowledge of what happened in the past allows both vertebrates and invertebrates to predict future outcomes by recalling previous experience. Although invertebrate and vertebrate brains share common principles at the molecular, cellular, and circuit-architectural levels, there are also obvious differences as exemplified by the use of acetylcholine versus glutamate as the considered main excitatory neurotransmitters in the respective central nervous systems. Nonetheless, across central nervous systems, synaptic plasticity is thought to be a main substrate for memory storage. Therefore, how brain circuits and synaptic contacts change following learning is of fundamental interest for understanding brain computations tied to behavior in any animal. Recent progress has been made in understanding such plastic changes following olfactory associative learning in the mushroom bodies (MBs) of Drosophila A current framework of memory-guided behavioral selection is based on the MB skew model, in which antagonistic synaptic pathways are selectively changed in strength. Here, we review insights into plasticity at dedicated Drosophila MB output pathways and update what is known about the plasticity of both pre- and postsynaptic compartments of Drosophila MB neurons.

Highly Bionic Neurotransmitter-Communicated Neurons Following Integrate-and-Fire Dynamics.

In biological neural networks, chemical communication follows the reversible integrate-and-fire (I&F) dynamics model, enabling efficient, anti-interference signal transport. However, existing artificial neurons fail to follow the I&F model in chemical communication, causing irreversible potential accumulation and neural system dysfunction. Herein, we develop a supercapacitively gated artificial neuron that mimics the reversible I&F dynamics model. Upon upstream neurotransmitters, an electrochemical reaction occurs on a graphene nanowall (GNW) gate electrode of artificial neurons. Charging and discharging the supercapacitive GNWs mimic membrane potential accumulation and recovery, realizing highly efficient chemical communication upon use of acetylcholine down to 2 × 10-10 M. By combining artificial chemical synapses with axon-hillock circuits, the output of neural spikes is realized. With the same neurotransmitter and I&F dynamics, the artificial neuron establishes chemical communication with other artificial neurons and living cells, holding promise as a basic unit to construct a neural network with compatibility to organisms for artificial intelligence and deep human-machine fusion.

Acetylcholine Use in Modern Cardiac Catheterization Laboratories: A Systematic Review.

Background: The use of acetylcholine for the diagnosis of vasospastic angina is recommended by international guidelines. However, its intracoronary use is still off-label due to the absence of safety studies. We aimed to perform a systematic review of the literature to identify adverse events related to the intracoronary administration of acetylcholine for vasoreactivity testing to fill this gap. Methods and results: We conducted a systematic review of observational studies and randomized controlled trials dealing with the intracoronary administration of acetylcholine. Articles were searched in MEDLINE (PubMed) using the MeSH strategy. Three independent reviewers determined whether the studies met the inclusion and exclusion criteria. A total of 434 articles were selected. Data concerning clinical characteristics, study population, acetylcholine dosage, and adverse effects were retrieved from the articles. Overall, 71,566 patients were included, of which only 382 (0.5%) developed one adverse event, and there were no fatal events reported (0%). Conclusions: Intracoronary administration of acetylcholine in the setting of coronary spasm provocation testing is safe and plays a central role in the evaluation of coronary vasomotion disorders, making it worthy of becoming a part of clinical practice in all cardiac catheterization laboratories.

Clinical use of acetylcholine in the cath lab, ready for prime time?

Clinical use of acetylcholine in the cath lab, ready for prime time?

Spasmogenic effect of a Solanummelongena leaf extract on guinea pig tracheal chains and its possible mechanism(s)

The methanol extract of fresh leaves of Solanum melongena L. (Solanaceae) was evaluated for its capacity to alter the tone of isolated, pre-contracted guinea pig tracheal chains, as well as for its possible mechanism(s) of action. Using serial dilutions between 0.0025 and 2.5 mg/mL, the extract was found to cause a dose-dependent increase in the force of muscle contraction. The EC 50 value was 0.46 ± 0.01 mg/mL. The concomitant use of acetylcholine 10 −5 M did not significantly affect the force of contraction induced by the extract. Histamine 10 −5 M added at about 40% to, and salbutamol 10 −6 M antagonized by about 30% its constrictive effect. Chlorpheniramine 10 −6 M, propanolol 10 −5 M, and nifedipine 10 −6 M did not significantly influence the extract-induced force of contraction, but atropine 3 × 10 −7 M reduced it by approximately 60%. These data suggest that the Solanum melongena extract exerted a bronchospasmogenic rather than a bronchospasmolytic effect, probably through muscarinic receptor stimulation.

Eye muscle surgery.

In the past year experimental studies have analyzed the ease with which specific sutures can be adjusted, have investigated ways to prevent adhesions in animal models, and have studied variations of the inferior oblique at the surgical capture site. Our knowledge of rectus extraocular muscle pulleys continues to improve, and the value of botulinum toxin type A in the treatment of several conditions has been further documented. New surgical techniques include slanted recessions of the lateral rectus muscles, combined monocular resection and bilateral anterior transposition of the inferior oblique, and intraoperative use of acetylcholine during inferior oblique myectomy. Favorable results have been reported after clinically important modifications to the superior oblique muscle silicone expander and anterior transposition of the inferior oblique procedures, as well as after bilateral inferior rectus muscle recession in dysthyroid ophthalmopathy. Conjunctival inclusion cysts, anterior segment ischemia despite microvascular dissection, and corneal topographic changes are reported as complications occurring after strabismus surgery. Recent publications discussing these issues are reviewed here.

Ambroxol Improves the Broncho-spasmolytic Activity of Clenbuterol in the Guinea-Pig

The effects of ambroxol on the spasmolytic action of clenbuterol were investigated on acetylcholine-induced bronchospasm in guinea-pigs. Ambroxol (50 mg kg-1 day-1) or vehicle was administered orally for 14 days. Approximately 45 min after the final dose on day 14, the animals were anaesthetized and the spasmolytic effects of clenbuterol (3, 6 or 12 micrograms kg-1 injected intravenously) were determined by use of acetylcholine (40 micrograms kg-1, i.v.)-induced bronchoconstriction. For both vehicle- and ambroxol-treated animals, a positive linear relationship was observed between the log-dose of clenbuterol and the percent inhibition of bronchospasm. The calculated ED25 of clenbuterol (i.e., the dose producing 25% inhibition of the acetylcholine-induced bronchospasm) was 3.98 micrograms kg-1 (3.29 to 4.82 micrograms kg-1, 95% confidence interval) in the presence of ambroxol and 5.81 micrograms kg-1 (4.98 to 6.79 micrograms kg-1) in the absence of ambroxol. The linear regressions with or without ambroxol differed from each other (P < 0.001) but ran parallel (covariance analysis), enabling us to calculate a relative potency, the value of which was 1.46 (1.16 to 1.84). These results demonstrate that the spasmolytic activity of clenbuterol is significantly improved in animals pretreated with ambroxol.

Emergency treatment of asthma.

The cholinergic component in the sympathetic innervation to the spleen was studied in dogs. This was accomplished by the use of hemicholinium (HC-3) to inhibit transmission in the chohinergic nerves and the use of reserpine and guanethidine to inhibit adrenergic function. The spleen responded normally to electrical stimulation of the splenic nerve at a time when cholinergic transmission was inhibited. These data support the concept of separate chohimiergic and adrenergic fibers in the splenic nerve rather than a cholinergic junction in the adrenergic fibers. The relationships between the cholinergic and adrenergic components associated with the splenic nerve were studied further by the use of acetylcholine and nicotine. Both of these components of this nerve were found to be involved in both the responses to nicotine and in a possible mechanism for the control of the tone of the splenic capsule. These data are dliscussed in relation to the hypothesis of local chohinergic-adrenergic interaction.

Use of acetylcholine (Ach) for spreading metaphase chromosomes and application to the cytogenetic analysis of human stomach cancers

Cytogenetic studies of biopsy specimens endoscopically obtained from gastric cancers were performed in our laboratory. The necessity for well-spread chromosomes for analysis has resulted in the development of a new technique, in which culture medium containing acetylcholine (Ach) is used; with this new technique, the number of metaphases of analyzable karyotypes was significantly increased (P < 0.01 compared with a previous method in which Ach was not used). The mean ratio of metaphase numbers of analyzable karyotypes in four cases in which Ach was used was 38.1 +/- 8.1%, a value more than four times the number in the seven cases in which Ach was not used. It is possible that Ach may decrease the viscosity of the cytoplasm in gastric cancer cells by disrupting microfilaments.

A review of coronary arteriography- and contrast media-induced ventricular fibrillation.

Since the first animal coronary arteriogram in 1933 there have been many innovations in techniques and contrast media. From 1933 through the late 1950s the procedures used involved nonselective aortic injections and the use of acetylcholine to slow the heart. The first selective coronary arteriogram in animals was performed by West, Kobayashi & Guzman in 1958 (45) and in 1959 Guzman & West (7) observed ventricular fibrillation with some media but not others. In 1967 Judkins (14) described the catheter designs for right and left coronary catheterizations that we still use today. In the 1970s and 80s many authors observed the ionic monomeric contrast media reduced plasma calcium causing fibrillation and myocardial depression. Supplementation of ionic media with calcium was shown to moderate these adverse effects. Almen's vision of low osmolality contrast media and the creation of metrizamide (1) stimulated the rapid development of monomeric and dimeric nonionic contrast media. The ionic dimeric medium ioxaglate also provided low osmolality. Digital frame grabbers and computers lead to the development of digital subtraction angiography and new applications of arteriography, frequently using dilute media. Unexpectedly, during prolonged right coronary arteriography in animals, dilute nonionic media were found to produce increased fibrillation as compared to dilute ionic media. The addition of sodium to nonionic media significantly reduced the incidence of fibrillation. Animal studies with the nonionic medium iodixanol supplemented with sodium and calcium (Visipaque) have demonstrated minimal incidences of fibrillation and myocardial depression.

EVALUATION OF RETINAL TOXICITY OF ACETYLCHOLINE IN RABBIT EYES

In vitreoretinal surgery, pupillary constriction may be required at the termination of a procedure especially if mechanical pupillary dilation was used in eyes filled with gas or silicone oil. A miotic agent instilled into the anterior chamber will sink and come into direct contact with retina in the aphakic or pseudophakic vitrectomized eye. Therefore, the retinal toxicity of acetylcholine, a miotic used for pupillary constriction, was studied. Eight Dutch pigmented rabbit eyes were vitrectomized, had air-fluid exchange, and were injected with a 20% mixture of SF6. Subsequently eyes were randomly selected to have injections of 0.75 ml of 10 mg/ml acetylcholine (Miochol, Iolab Corp., Claremont CA) versus 0.75 ml of lactated Ringer's solution. Short-term (2 weeks) and long-term (6 weeks) retinal toxicity was assessed by ophthalmoscopy, electroretinogram, and histology by light and electron microscopy at both times. Ophthalmoscopy, electroretinographic tracings, histology, and electron microscopy disclosed no significant abnormalities. Acetylcholine does not appear to have significant retinal toxicity even when undiluted solutions are in direct contact with the retina. We therefore postulate that intraoperative use of acetylcholine in previously vitrectomized eyes filled with gas or silicone is safe.

Die Wirkung von intraokulär appliziertem Azetylcholin und Carbachol auf das postoperative Druckverhalten nach Kataraktoperationen

In a consecutive series of 90 patients we examined the effect of intracameral acetylcholine and carbachol on intraocular pressure following extracapsular cataract surgery. In all cases phacoemulsification and implantation of a folded polyhema intraocular lens under healon was performed. After evacuation of the viscoelastic substance from the capsular bag behind the inserted lens and wound suturing we instilled 0.5 ml 1% acetylcholine, 0.5 ml 0.01% carbachol or 0.5 ml balanced salt solution respectively into the anterior chamber. Without the influence of antiglaucomatous drugs applanation tonometry was performed 6 and 18 hours postoperatively. When compared with preoperative values intraocular pressure decreased in the carbachol group (-2.8 mm Hg) but increased in the acetylcholine group (+0.6 mm Hg) and control group (+4.7 mm Hg). 18 hours postoperatively the mean change was -3.0 mm Hg in the carbachol group, +0.8 mm Hg in the acetylcholine group and +2.3 mm Hg in the control group. Intraocular pressure exceeding 22 mm Hg at 6 hours was observed in 33% of the control group and 13% of the acetylcholine group but none of the carbachol group. At 18 hours intraocular pressure was still elevated in 13% of the control group, 10% of the acetylcholine group and 3% of the carbachol group. Reviewing our results we conclude that the evacuation of viscoelastic substances from the capsular bag behind the implanted lens reduces the incidence of pressure rises in the early postoperative period. This effect can be enhanced by the use of acetylcholine and, the more potent, carbachol.

Evidence in vivo of an intact endothelial function in internal mammary arteries before and after implantation as coronary grafts

To evaluate the effect of grafting on the endothelial function of the internal mammary artery (IMA) in patients with coronary artery disease, the response to acetylcholine was examined in native IMA and in IMA grafts, and was compared with the response in the coronary arteries. Fourteen patients were examined, including 6 patients with advanced coronary artery disease without previous surgery or angioplasty (group 1), and 8 patients with IMA grafts 3 to 35 months after surgery (group 2). Acetylcholine (7 to 700 nmol/min) was infused selectively into either the left anterior descending coronary artery and the native IMA, or into the graft on the left anterior descending coronary artery. The effect on vessel diameters was assessed by quantitative angiography. The segments evaluated in both groups did not show angiographic evidence of significant local atherosclerosis. Seventy-eight percent of the coronary artery segments in group 1 and 91% in group 2 were contracted by acetylcholine. Native IMA and IMA grafts were not contracted by acetylcholine. There was a marked difference in a the response of graft segments and the adjacent coronary segments in group 2 (acetylcholine, 700 nmol/min: 100.6% ± 12.9% of control vs. 64.3% ± 32.4%; P < 0.001). By use of acetylcholine as an indicator of endothelial dysfunction it was concluded that the native IMA had intact endothelial function, in contrast to the coronary arteries of the same patients. Several months after surgery, the IMA still showed no evidence of an impaired endothelium-dependent vascular response.

Functional abnormalities of experimental autogenous vein graft neoendothelium.

When a vein is grafted into the arterial circulation, the endothelium of the graft is damaged. Regeneration of an intact neoendothelium occurs, but the functional properties of this surface have not been clarified. In this study, the functional integrity of the neoendothelium of veins grafted into the carotid artery of the rabbit was assessed through the use of acetylcholine and histamine to stimulate the production of the important endothelium-derived relaxing factor (EDRF). Control veins, precontracted with norepinephrine [10(-5) M], relaxed after exposure to acetylcholine [( 10(-7) M], 42.4% +/- 6.4%, p = 0.008) and histamine [( 10(-6) M], 30.6% +/- 4.3%, p = 0.03). This relaxation response was abolished after mechanical removal of the endothelium. By contrast, neither acetylcholine nor histamine caused an endothelium-dependent relaxation in the vein grafts, even though scanning electron microscopy demonstrated the presence of a morphologically intact endothelium. However, addition of stabilized EDRF purified from cultured endothelial cells induced relaxation of the vein grafts (35.8% +/- 3.6%, p = 0.002). These data indicate that vein graft endothelium is unable to produce EDRF in response to exposure to acetylcholine or histamine. The inability to produce this potent smooth muscle cell relaxing factor and anti-aggregatory substance may be a predisposition to vein graft failure.

Use of acetylcholine to measure total vascular pressure-volume relationship in dogs.

To define total vascular capacitance, we used acetylcholine to arrest the heart and measured mean circulatory filling pressure (MCFP) during controlled hemorrhage and volume loading in 12 splenectomized dogs after ganglion blockade with hexamethonium. We also examined the gross pathological and histological changes in the lungs. Controlled hemorrhage (n = 12) of 5 and 10 ml/kg decreased MCFP from 6.8 +/- 0.1 to 4.9 +/- 0.3 and 3.6 +/- 0.2 mmHg, respectively. Volume loading of 5 (n = 8) and 10 ml/kg (n = 4) increased MCFP to 9.3 +/- 0.2 and 12.1 +/- 0.1 mmHg, respectively. At MCFPs below 5 mmHg, the pressure (P)-volume (V) relationship was not linear [(P = P0ekV, where k is slope of ln (MCFP) vs. V, k = 0.061, R2 = 0.998]. At MCFPs between 5 and 12 mmHg, the pressure-volume relationship was linear (slope = 0.479 mmHg.ml-1.kg-1, R2 = 0.992) and total vascular compliance was 2.09 ml.mmHg-1.kg-1. There were no changes in heart rate, cardiac output, right atrial, pulmonary artery, and pulmonary artery wedge pressures when values at base line were compared with those measured 15 min after each arrest. There were no changes in arterial gas measurements or acid-base balance, and there was no evidence of atelectasis or interstitial or intra-alveolar edema. We conclude that the total body pressure-volume relationship in the presence of ganglion blockade had a nonlinear configuration. The use of acetylcholine to arrest the heart, four times with hexamethonium in reflex-blocked animals, did not result in changes in hemodynamics or pulmonary function.

The Mouse Parotid Gland Preparation: An in vivo Pharmacological Tool

The effects of several autonomic agents on total protein, amylase, RNase, calcium, potassium, and sodium levels and also on flow rate of mouse parotid saliva were investigated during the process of evaluating the in vivo mouse parotid gland preparation as a pharmacological tool. Acetylcholine and pilocarpine were used as secretagogues and produced different sequential patterns of sodium and enzyme levels secreted in mouse parotid saliva. Additionally, propranolol treatment was able to alter amylase and sodium levels produced by pilocarpine stimulation significantly, as well as alter calcium levels produced by both acetylcholine and pilocarpine stimulation. Phentolamine treatment resulted in higher amylase levels with both acetylcholine and pilocarpine stimulation. The use of acetylcholine as a secretagogue allows one to perform in vivo anticholinergic experiments which alter flow rates without significantly altering protein or ion levels secreted in mouse parotid saliva.

Clinical experience in the intra-ocular use of acetylcholine.

Clinical experience in the intra-ocular use of acetylcholine.

Pharmacology of Respiratory Distress

We found the "Preliminary Report on the Pulmonary Hypoperfusion Syndrome" by Chu, et al. (Pediatrics 35:733) a most erudite and provocative approach to better understanding of neonatal respiratory distress. We were particularly interested in the use of acetyl choline to dilate the pulmonary vessels. Although the authors used only acetyl choline, oxygen, and sodium bicarbonate to relieve vasoconstriction, they suggest that "it may be that another cholinergic, antiadrenergic, or gangliono-plegic drug will be more convenient and successful."

Stimulation of Caudate Nucleus

Studies employing electrical stimulation in chronically prepared, freely moving animals have given disappointingly little information about the functions of the caudate nucleus. In those instances in which positive motor responses have been reported, 1,2,7 there is still the problem of refuting or confirming Kinnier Wilson's arguments that the effects are owing to excitation of fibers of passage. 19 In investigations of the limbic system, we have employed local chemical stimulation of the brain as an adjunct to electrical stimulation. 13 We have favored the use of acetylcholine or related drugs because acetylcholine is a naturally occurring substance in the brain and may function in the central nervous system as a neural transmitter. The use of cholinergic stimulation for exploration of the functions of the caudate seemed particularly appropriate for several reasons. 1. Such stimulation ostensibly does not excite nerve fibers and would therefore not activate fibers of passage. 2. Similarly,

Muscle receptor organs in some decapod crustacea

The presence of muscle receptor organs was determined in the abdomen of ten species of decapod Crustacea. These were Pandalus danae, Paracrangon echinata, Crago franciscorum, Eualus sp. (tribe Caridea) belonging to the Natantia, and Munida quadrispina (tribe Galatheidea), Upogebia pugettensis, Callianassa gigas (tribe Thalassinidea), Paragus aleuticus, P. alaskensis, P. kennerlyi (tribe Paguridea) belonging to the Reptantia. Responses of the sensory neurons were obtained by flexion of the joints of isolated abdomens, and in some cases by stretching the organs themselves or by the use of acetylcholine. All species yielded slowly-adapting responses and some gave also fast-adapting responses. Anatomical examination was used to confirm the existence of the organs in a number of species. In one species of true crab, Cancer magister (tribe Brachygnatha), no evidence was obtained, either physiologically or anatomically, for the presence of muscle receptor organs. The known distribution of muscle receptor organs in higher Crustacea is tabulated and the possible widespread occurrence of such organs in the Crustacea as a whole is discussed.