Acetylcholine (ACh) is a chemical messenger that carries signals between nerve cells in the brain and body. In horses, acetylcholine is a vital neurotransmitter, crucial for muscle function, the parasympathetic nervous system, and various other bodily functions. This page compiles peer-reviewed research studies and scholarly articles that examine the role, mechanisms, and effects of acetylcholine in equine physiology and health.
Olson LE, Perkowski SZ, Mason DE, Muir WW.Strips of trachealis muscle were dissected from the mid-cervical portion of the trachea from horses that were free of respiratory tract disease. The epithelium and mucosa were removed from one group of tissues and were left intact in a second group of tissues. Each tissue was suspended in a bath filled with Krebs-bicarbonate solution that was aerated with 5% CO2 in oxygen and maintained at 37 degrees C. Isometric tension was continuously recorded. The contractile response to square-wave electrical stimulations increased as frequency (3, 5, 10, 15, 20, 25, and 30 Hz), voltage (10, 15, 18, and 2...
Olson LE, Perkowski SZ, Mason DE, Muir WW.Strips of trachealis muscle were dissected from the midcervical portion of the trachea of horses that were free of respiratory tract disease, and the overlying epithelium and mucosa were removed. Muscle strips were suspended in tissue baths that were filled with Krebs-bicarbonate solution, aerated with 5% CO2 in oxygen and maintained at 37 C. Isometric tension was continuously recorded. The increase in active isometric tension was concentration dependent when acetylcholine (10(-9) to 10(-4) M) or histamine (10(-9) to 10(-4) M) was added to the tissue baths in 0.5-logarithmic increments. When t...
Hildebrand SV, Hill T, Holland M.To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental ...
Mason DE, Muir WW, Olson LE.Smooth muscle strips from the midcervical portion of the trachea and bronchial smooth muscle strips from third-generation airways of horses were placed in tissue baths, and isometric contractile force was measured. Active force was measured in response to electrical stimulation and exogenous acetylcholine. Square-wave electrical stimuli were applied at various voltages (10, 12, 15, 18, 20, 25 V), frequencies (3, 5, 10, 15, 20, 25, 30 Hz), and pulse durations (0.2, 0.5, 1.0, 1.5, 2.0 ms). Isometric contractile force increased as voltage, frequency, and pulse duration increased. Maximal contract...
Baxter GM, Tackett RL, Moore JN.Palmar digital arteries and veins removed surgically from healthy horses under general anesthesia were cut into 4 mm vascular rings, suspended in tissue baths, and attached to force displacement transducers for continuous measurement of vascular tension. In vitro vascular responses were determined for acetylcholine, acepromazine, isoxsuprine hydrochloride (isoxsuprine), prostaglandin E2 (PGE2), and prostaglandin I2 (prostacyclin). After preconstriction with norepinephrine hydrochloride (norepinephrine), or prostaglandin F2 alpha (PGF2 alpha), the concentrations needed to produce 50% maximum re...
Hildebrand SV, Arpin D.Neuromuscular and cardiovascular effects of atracurium, a nondepolarizing neuromuscular blocking agent, were evaluated in 10 halothane-anesthetized adult horses. Hind limb digital extensor tension (hoof twitch) was measured with a strain gauge to quantitate the muscle relaxant effects of atracurium. Response of facial muscles was compared with hoof twitch. Five injections of atracurium were given. Initial mean (+/- SEM) dosage of 0.07 +/- 0.01 mg of atracurium/kg of body weight caused 98.6 +/- 0.8% reduction of the preinjection hoof twitch. Subsequent dosages of 0.04 +/- 0.003 mg/kg induced a ...
Kay PH, Dawkins RL, Bowling AT, Bernoco D.A cDNA probe to the alpha subunit of the murine acetylcholine receptor was used to demonstrate restriction fragment length polymorphism in an acetylcholine receptor gene in the horse. Three different patterns of polymorphism have been observed with fragment sizes of 4.3 and 2.9 kilobases (kb) (pattern 1), 4.3 and 2.5 kb (pattern 2) and 4.3, 2.9 and 2.5 kb (pattern 1,2). Analysis of a three generation pedigree has suggested that patterns 1 and 2 represent two allelic forms of the gene encoding the alpha subunit of the acetylcholine receptor. These data provide a basis for the examination of the...
Hildebrand SV, Howitt GA, Arpin D.Atracurium besylate, a recently developed, intermediate-duration acting, neuromuscular-blocking agent, was given to 15 halothane-anesthetized ponies to produce surgical relaxation (95% to 99% reduction of hoof twitch). All 15 ponies were given 3 injections; 8 of the 15 ponies were given 2 additional injections. Initial dosage of 0.11 +/- 0.01 mg/kg (mean +/- SD) and all subsequent injections of 0.052 mg/kg produced desired relaxation. Paralysis phase (maximum twitch reduction to 10% twitch recovery) lasted 24 +/- 5 minutes for the initial injection. Paralysis from subsequent injections lasted ...
Costa G, Labadia A, Garcia-Sacristan A.The effects of verapamil, a calcium antagonist agent, were studied on smooth muscle preparations of the lower urinary tract of horses. Verapamil (2 X 10(-4) to 2 X 10(-8) M) relaxed the ureter, urethra and urinary bladder preparations contracted by potassium (127 mM), L-noradrenaline (2 X 10(-5) M), histamine (2 X 10(-5) M) and acetylcholine (2 X 10(-5) M). These results allow the conclusion that verapamil has a dose-dependent relaxing effect on smooth muscle of the lower urinary tract.
Hildebrand SV, Howitt GA.Efficacy of neostigmine (0.04 mg/kg of body weight) and edrophonium (1 mg/kg), as antagonists for pancuronium neuromuscular blockade in halothane-anesthetized ponies, was evaluated. Neostigmine and edrophonium were satisfactory antagonists, with edrophonium having a significantly (P less than 0.01) more rapid onset of action than did neostigmine. Muscarinic activity of neostigmine and edrophonium was also evaluated. Neither antagonist was administered with atropine. Gastrointestinal effects, increased salivation, and increased airway secretions were minimal with edrophonium, but were marked af...
Makhaeva GF, Shataeva GA, Iankovskaia VL, Fetisov VI, Loshadkin NA.The interaction of human erythrocyte acetylcholinesterase, horse serum butyrylcholinesterase and rat liver carboxylesterase with insecticides (RO)2P(O)SCH(COOEt)SP(O)(OR)2 (I) and (RO)2P(O)SCH(COOEt)OP(S)(OR)2 (II) was studied. The type I and II compounds were not hydrolyzed by carboxylesterase and inhibited the esterases irreversibly. A complex pattern of inhibition of acetylcholinesterase and butyrylcholinesterase by these compounds was caused by kinetically-manifested formation of an enzyme-inhibitor complex. The compounds I and II were more selective towards butyrylcholinesterase than towa...
Robinson NE, Dabney JM, Weidner WJ, Jones GA, Scott JB.The digital circulation was isolated in 12 ponies under pentobarbital anesthesia. Blood flow was either controlled by a pump or measured under natural perfusion. The responses to rapid changes and stoppages of blood flow indicated no evidence of autoregulation or reactive hyperemia. Local administration of acetylcholine, histamine, and prostaglandins E1 and E2 decreased prevenous resistance, whereas epinephrine and serotonin caused prevenous constriction. Large doses of epinephrine and serotonin decreased venous caliber. The effects of prostaglandins A1 and F2alpha were variable. The equine di...
Kay PH, Dawkins RL, Bowling AT, Bernoco D.A cDNA probe to the alpha subunit of the murine acetylcholine receptor was used to demonstrate restriction fragment length polymorphism in an acetylcholine receptor gene in the horse. Three different patterns of polymorphism have been observed with fragment sizes of 4.3 and 2.9 kilobases (kb) (pattern 1), 4.3 and 2.5 kb (pattern 2) and 4.3, 2.9 and 2.5 kb (pattern 1,2). Analysis of a three generation pedigree has suggested that patterns 1 and 2 represent two allelic forms of the gene encoding the alpha subunit of the acetylcholine receptor. These data provide a basis for the examination of the...
Hildebrand SV, Hill T, Holland M.To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental ...
Zhang XY, Zhu FX, Robinson NE.To investigate the effects of changes in intracellular cAMP on alpha 2-adrenoceptor (AR)-induced inhibition of airway acetylcholine (ACh) release, we examined the effects of the alpha 2-AR agonist clonidine on electrical field stimulation-evoked ACh release from equine tracheal parasympathetic nerves before and after treatment with 8-bromo-cAMP or forskolin. We also tested whether charybdotoxin (ChTX)- or iberiotoxin (IBTX)-sensitive Ca(2+)-activated K+ channels mediate alpha 2-AR-induced inhibition by examining the effect of clonidine in the absence and presence of ChTX or IBTX on ACh release...
Wang ZW, Yu MF, Robinson NE, Derksen FJ.The present study was conducted to determine if acetylcholine (ACh) release from airway cholinergic nerves is increased and if modulation of ACh release by prejunctional receptors is altered in horses with heaves, an obstructive airway disease characterized by airway inflammation and bronchospasm. Trachealis strips and bronchial segments of normal horses and horses affected with heaves were suspended in 2-ml tissue baths. ACh release was induced by electrical field stimulation and the bath ACh content was measured by high performance liquid chromatography (HPLC) with electrochemical detection....
Baxter GM.Low doses of endotoxin cause vasoconstriction and hypoperfusion of the digit, small intestine, and cecum in horses. To determine the potential cause of these vascular alterations, in vitro vascular responses of palmar digital arteries and veins were determined in 8 horses after intravenous (IV) infusion of 1 L 0.9% NaCl (control) and 0.1 microgram/kg Escherichia coli 055:B5 endotoxin in 1 L of 0.9% NaCl (endotoxin-treated). Vessels were surgically removed under general anesthesia, cut into 4-mm vascular rings, suspended in tissue baths, and attached to force displacement transducers for measur...
LeBlanc PH, Broadstone RV, Derksen FJ, Robinson NE.Distal airway segments (ID, 3 to 4 mm; length, 5 mm) from 2 groups of horses were isolated and suspended in tissue baths filled with Krebs solution, aerated with 5% CO2 in oxygen and maintained at 37 degrees C. Responses to exogenous acetylcholine, isoproterenol, or electrical field stimulation were compared. Control horses (n = 30) had no history of recurrent airway obstruction, whereas principal horses (n = 15) had recurrent airway obstruction and were studied during an acute episode of airway obstruction. Although the distal airways contracted in response to the cumulative half-logarithmic ...
Baxter G.Endotoxin given in vivo has been shown to inhibit endothelial dependent relaxation, and augment adrenergic (norepinephrine) contractions in isolated palmar digital arteries of horses. A study, using tumor necrosis factor (TNF) in vitro, was performed to determine the possible cause of these vascular alterations. Palmar digital arteries were surgically removed from 6 horses under general anesthesia, cut into 4-mm vascular rings (4 segments/horse), suspended in tissue baths, and attached to force displacement transducers for measurement of vascular tension. Four in vitro treatment groups were ev...
McGorum BC, Milne AJ, Tremaine WH, Sturgeon BP, McLaren M, Khan F.A combined laser Doppler flowmetry and iontophoresis (LDFI) technique, used routinely to assess human microvascular function, was evaluated as a noninvasive technique for assessment of equine microvascular function, to facilitate the study of diseases such as laminitis. Baseline and vasoactive agonist-induced (acetylcholine and nitroprusside) microvascular flux was quantified at 2 sites (on the dorsal pastern adjacent to the coronary band and over the gluteals) in 6 clinically normal horses on 5 or 6 separate occasions under standardised conditions. Both agonists significantly increased microv...
Makhaeva GF, Shataeva GA, Iankovskaia VL, Fetisov VI, Loshadkin NA.The interaction of human erythrocyte acetylcholinesterase, horse serum butyrylcholinesterase and rat liver carboxylesterase with insecticides (RO)2P(O)SCH(COOEt)SP(O)(OR)2 (I) and (RO)2P(O)SCH(COOEt)OP(S)(OR)2 (II) was studied. The type I and II compounds were not hydrolyzed by carboxylesterase and inhibited the esterases irreversibly. A complex pattern of inhibition of acetylcholinesterase and butyrylcholinesterase by these compounds was caused by kinetically-manifested formation of an enzyme-inhibitor complex. The compounds I and II were more selective towards butyrylcholinesterase than towa...
Hildebrand SV, Howitt GA.Efficacy of neostigmine (0.04 mg/kg of body weight) and edrophonium (1 mg/kg), as antagonists for pancuronium neuromuscular blockade in halothane-anesthetized ponies, was evaluated. Neostigmine and edrophonium were satisfactory antagonists, with edrophonium having a significantly (P less than 0.01) more rapid onset of action than did neostigmine. Muscarinic activity of neostigmine and edrophonium was also evaluated. Neither antagonist was administered with atropine. Gastrointestinal effects, increased salivation, and increased airway secretions were minimal with edrophonium, but were marked af...
Baxter GM, Tackett RL, Moore JN.Palmar digital arteries and veins removed surgically from healthy horses under general anesthesia were cut into 4 mm vascular rings, suspended in tissue baths, and attached to force displacement transducers for continuous measurement of vascular tension. In vitro vascular responses were determined for acetylcholine, acepromazine, isoxsuprine hydrochloride (isoxsuprine), prostaglandin E2 (PGE2), and prostaglandin I2 (prostacyclin). After preconstriction with norepinephrine hydrochloride (norepinephrine), or prostaglandin F2 alpha (PGF2 alpha), the concentrations needed to produce 50% maximum re...
Olson LE, Perkowski SZ, Mason DE, Muir WW.Strips of trachealis muscle were dissected from the midcervical portion of the trachea of horses that were free of respiratory tract disease, and the overlying epithelium and mucosa were removed. Muscle strips were suspended in tissue baths that were filled with Krebs-bicarbonate solution, aerated with 5% CO2 in oxygen and maintained at 37 C. Isometric tension was continuously recorded. The increase in active isometric tension was concentration dependent when acetylcholine (10(-9) to 10(-4) M) or histamine (10(-9) to 10(-4) M) was added to the tissue baths in 0.5-logarithmic increments. When t...
Hajek P, Ungemach FR, Abraham G.Muscarinic acetylcholine receptor (mAChR)-mediated guanine nucleotide-binding regulatory protein (G protein) activation and the functional interaction between receptors and the respective G proteins were investigated using an agonist-induced [(35)S]guanosine-5'-O-(gamma-thiotriphosphate) ([(35)S]GTPgammaS)-binding approach in membranes of 3 native equine airway segments (trachea, bronchus and lung), which differ tremendously in mAChR density and subtype distribution; especially subtypes that couple negatively to adenylyl cyclase through G(i/0) proteins, i.e. M(2) receptors. The assay was initi...
Nissen SD, Saljic A, Carstensen H, Braunstein TH, Hesselkilde EM, Kjeldsen ST, Hopster-Iversen C, D'Souza A, Jespersen T, Buhl R.Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone. Unassigned: To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M) and the G protein-gated inwardly rectifying K (GIRK4) channel that mediates the cardiac current. Unassigned: Eighteen horses with a low burden of second-degree AV block (median 8 block per 20 h, IQR: 32 per 20 h) were assign...
