Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vasoactive properties of substance P (SP) were studied in isolated rabbit pulmonary artery (PA) segments in vitro. In the absence of active base-line tone, noncumulative administration of SP (10(-11) to 10(-4) M) produced dose-dependent increases in PA tension. The peak isometric tension (Tmax) with SP was similar to the Tmax response to epinephrine; however, the doses of the agonist producing a threshold contraction and 25% of Tmax (ED25) were significantly lower for SP. In the presence of active base-line tone, induced by epinephrine or 5-hydroxytryptamine, SP produced transient PA relaxation which was directly related to the magnitude of the precontracted PA tension. Blockade of neurotransmission with tetrodotoxin (1 microgram/ml) and antagonists to alpha 1-adrenergic and histamine receptor binding had no effect on the contractile response to SP. On the other hand, PA contraction to an ED50 dose of SP was 1) inhibited by a mean of 33 +/- 10% (SE) following pretreatment with the cholinesterase inhibitor, neostigmine (10(-6) M) and 2) augmented by 52 +/- 21% with the cholinergic antagonist, atropine (10(-4) M). The latter also completely blocked the relaxation response to SP in precontracted PA. Similarly, removal of the PA endothelium also abolished the relaxation response to SP. In contrast, SP-induced contraction was markedly inhibited by the cyclooxygenase inhibitor, meclofenamate (1 microgram/ml), as well as the SP antagonist, D-Pro2, D-Trp7,9-SP.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Vasoactive effects of substance P on isolated rabbit pulmonary artery. 258 Aug 23

To elucidate the mechanism underlying temperature-induced changes in airway cholinergic contractility, the effects of organ bath cooling were evaluated in isolated rabbit airway smooth muscle (ASM) segments isometrically contracted with methacholine (METH) (10(-8)-10(-3) M) and electrical field stimulation (ES), wherein the ES stimulus frequency was varied between 1 and 100 Hz. Cooling from 37 to 25 degrees C produced systematic increases (P less than 0.01) in isometric tension at various administered doses of METH and at different levels of ES. Since the potentiated contractions to ES significantly exceeded (P less than 0.001) the corresponding increases in METH-induced contractility, we evaluated whether the latter was attributed to temperature-mediated changes in intrinsic airway neuronal acetylcholine (ACh) release. Accordingly, the effects of ASM cooling were independently determined before and after inhibition of the Na+-K+ electrogenic pump with ouabain (10(-5) M), and depletion of intrinsic neuronal ACh stores with hemicholinium-3 (HC-3) (10(-3) M). In the presence of either ouabain or HC-3 the above responses to temperature reduction were reversed, and airway cooling was associated with abrupt relaxation of ASM segments precontracted with METH. In contrast, neither inhibition of cyclooxygenase products with indomethacin (10(-6) M) nor cholinesterase inhibition with neostigmine (10(-3) M) notably influenced the ASM responses to organ bath cooling. Thus these findings demonstrate that 1) both METH-induced and neurally mediated cholinergic contractility are augmented during airway cooling; 2) the potentiated cholinergic responses are attributed to enhanced presynaptic release of ACh at the airway neuromuscular junction.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effects of temperature on cholinergic contractility of rabbit airway muscle. 332 12

1. Recordings of evoked postganglionic compound action potentials (CAPs) evoked by preganglionic stimulation were obtained from guinea pig superior cervical ganglia (SCGs) in vitro to study the effects of specific antigen challenge on ganglionic synaptic transmission. SCGs were removed from guinea pigs actively sensitized to ovalbumin. 2. Exposing SCGs from sensitized animals to the sensitizing antigen (0.01-10 micrograms/ml) for 5 min produced a sustained increase in the magnitude of the evoked CAP unaccompanied by a change in the preganglionic volley. Nonsensitizing antigens were ineffective. Also ineffective were antigens applied to nonsensitized SCG. This persistent antigen-induced increase in synaptic transmission was designated antigen-induced long-term potentiation (LTP) (A-LTP) because its duration (> 30 min) greatly outlasted posttetanic potentiation (PTP) in this ganglion. 3. A-LTP and neurogenic LTP (N-LTP) were observed to coexist in the same ganglion; the presence of one form of synaptic plasticity did not preclude the development of the other. Both phenomena were influenced by presynaptic factors: prolonged (2 h, 40 Hz) repetitive presynaptic stimulation abolished A-LTP or N-LTP but did not affect PTP. 4. By contrast to N-LTP, which requires a brief presynaptic tetanus, A-LTP could be triggered over a wide range of presynaptic stimulation (0.016-3 Hz) or even in the absence of presynaptic stimulation. 5. The amplitude and duration of A-LTP were not significantly affected by 1) H1, H2, or H3 histamine receptor antagonists added before or after antigen challenge; 2) the presence of saturating concentrations of histamine (100-300 microM); 3) the presence of specific or nonspecific lipoxygenase inhibitors or a selective cyclooxygenase inhibitor; or 4) blockade of alpha- or beta-adrenergic receptors, 5-HT3 receptors, muscarinic receptors, or glutamate receptors, or inhibition of acetylcholinesterase or protein synthesis. 6. Our results indicate that specific antigen challenge of isolated sympathetic ganglia activates resident mast cells to release substances that initiate a novel form of synaptic plasticity, an activity-independent and long-lasting increase in synaptic efficacy.
...
PMID:Antigen-induced long-term potentiation of nicotinic synaptic transmission in the superior cervical ganglion of the guinea pig. 762 97

Polyclonal antisera and six distinct monoclonal antibodies (mAbs) were raised against constitutive cyclooxygenase (COX-1) purified from ram seminal vesicles. Immunoblotting experiments revealed that the polyclonal antisera and 4 of the mAbs strongly recognized human COX in platelet extracts. Different two-site immunometric assays of ram COX-1 were established using different combinations of mAbs. The assays were performed in 96-well microtiter plates coated with one mAb, with another mAb (covalently labeled with acetylcholinesterase (AChE)) as tracer. One combination (solid phase CX-101 + CX-105-AChE) exhibited the best sensitivity, with significant detection of concentrations as low as 23 pg/ml (0.3 fmol/ml of sheep COX-1). Unfortunately, this assay poorly cross-reacted with human COX-1 from platelet extracts. Another combination (solid phase CX-111 + CX-110-AChE) exhibited good recognition of human COX-1 but poor cross-reactivity with ram COX-1. Finally, purified anti-COX-1 IgG coated and CX-110-AChE were chosen as the best compromise since both good sensitivity (limit of detection, 113 pg/ml of ram COX-1) and significant cross-reactivity between COX-1 from both species were observed. In parallel, polyclonal antibodies were raised in rabbits against a peptide of 12 amino acids corresponding to the aminoterminal part of human COX-1. These polyclonal antibodies were affinity-purified and used in development of another two-site immunometric assay of COX-1 with CX-110-AChE as tracer. These two assays were used to analyze the COX-1 content of human platelets and cultured human umbilical vein cells (HUVEC). The results obtained with each assay were compared in terms of sensitivity and specificity. The validity of both assays was checked by analyzing platelets and HUVEC extracts previously fractionated by molecular sieve chromatography.
...
PMID:Immunological studies of human constitutive cyclooxygenase (COX-1) using enzyme immunometric assay. 785 74

To determine whether N- or L-type Ca2+ channels mediate acetylcholine (ACh) release from airway parasympathetic nerve endings, we compared the effects of omega-conotoxin (N-type inhibitor) and nifedipine (L-type inhibitor) on electrically evoked release of ACh in guinea pig trachea. Reconnected segments of guinea pig trachea were mounted in organ baths containing Krebs-Henseleit buffer, indomethacin (10 microM) to inhibit cyclooxygenase, neostigmine (1 microM) to inhibit acetylcholinesterase, and atropine (0.3 microM) to inhibit muscarinic autoreceptors, as well as phentolamine and propranolol to inhibit adrenergic receptors. After electrical field stimulation (EFS), aliquots of buffer were removed, and ACh was measured directly by high-performance liquid chromatography with electrochemical detection. Tracheas were stimulated for 10-min periods at a frequency of 5 Hz, and ACh release was measured for five separate periods (S1-S5) after treatment with increasing concentrations of omega-conotoxin or vehicle alone (acetic acid). Thirty minutes was allowed between stimulation periods. We found that EFS-evoked release of ACh was inhibited by omega-conotoxin in a concentration-dependent manner [mean effective concentration (EC50) approximately 8 nM] but was unaffected by vehicle treatment. In other experiments, ACh release was measured for two separate periods (S1 and S2), and between periods tracheas were treated with omega-conotoxin (1 microM), nifedipine (10-100 microM), tetrodotoxin (TTX), or buffer containing low (0.8 mM) Ca2+. ACh release was 12 +/- 2 (mean +/- SE) and 3 +/- 0.3 pmol.mg protein-1.min-1 before and during omega-conotoxin (n = 5, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:N-type, omega-conotoxin-sensitive Ca2+ channels mediate electrically evoked release of ACh in guinea pig trachea. 839 14

Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) activities were detected in bronchial and bronchial epithelial cell homogenates of the pig. In the bronchial homogenates, the maximal upstroke velocity (Vmax) of AChE and the maximal velocity after second substrate fixation (Vss) of BChE were 5.70 +/- 0.46 and 7.87 +/- 0.81 mU/mg protein, respectively. In the epithelial cell homogenates, a smaller amount of cholinesterase (ChE) was found: Vmax was 0.62 +/- 0.29 and Vss was 1.56 +/- 0.33 mU/mg protein for AChE and BChE, respectively. AChE activity was increased by 21 +/- 5% in the bronchial homogenates and by 54 +/- 14% in the epithelial cell homogenates, when intact bronchial segments were incubated with a cyclooxygenase inhibitor, indomethacin (INDO). These results suggest that prostanoids may be involved in the regulation of AChE activity in pig airways.
...
PMID:Cholinesterase activity in pig airways and epithelial cells. 924 50

The aim of the present study was to commence a characterisation of some of the basic pharmacological properties of venom from the soldierfish (Gymnapistes marmoratus). Soldierfish venom was prepared by extraction into 10% glycerol and centrifugation to remove insoluble material. Protein content was determined and venom concentrations were expressed as microgram venom protein. Soldierfish venom (0.5-15 micrograms/ml) produced concentration-dependent contractile responses in guinea-pig isolated ileum (GPI) and longitudinal smooth muscle (LSM) preparations. The muscarinic receptor antagonist atropine (10 nM) significantly inhibited responses of LSM to soldierfish venom (2.5 micrograms/ml). Responses to soldierfish venom (4-5 micrograms/ml) in GPI were not significantly affected by the ganglion-blocking drug mecamylamine (10 microM) or by incubation with blood cholinesterase. The cyclooxygenase inhibitor indomethacin (2 microM) significantly inhibited responses to soldierfish venom (2.5 micrograms/ml) in LSM. Neither the thromboxane A2/prostaglandin H2 receptor antagonist GR32191B (1 microM) nor the leukotriene receptor antagonist SB205312 (10 nM) significantly affected responses to soldierfish venom (5 micrograms/ml) in GPI. Responses to soldierfish venom (2.5-5 micrograms/ml) were not significantly inhibited by the histamine receptor antagonist mepyramine (0.5 microM), the angiotensin-converting enzyme inhibitor captopril (2 microM) or the neurokinin-1 receptor antagonist CP-99,994 (0.1 microM) in LSM. The angiotensin AT1 receptor antagonist EXP3174 (0.1 microM) also failed to inhibit significantly the responses to soldierfish venom (5 micrograms/ml) in GPI. A fluorometric assay for the detection of 5-hydroxytryptamine (5-HT) and related compounds indicated a level in soldierfish venom of 1.60 +/- 0.01 ng of 5-HT-like substance per microgram venom protein. Soldierfish venom (0.5-10 micrograms/ml) produced concentration-dependent contractile responses in rat isolated stomach fundus strips, and these responses (2.5 micrograms/ml) were significantly inhibited by the 5-HT1/5-HT2 receptor antagonist methysergide (0.1 microM). These results suggest that soldierfish venom may stimulate the release of acetylcholine to act at muscarinic receptors on guinea-pig gastrointestinal smooth muscle. The venom also appears to be causing the release of cyclooxygenase products, such as prostaglandins, and contains 5-HT, or a 5-HT-like substance, that acts directly at 5-HT receptors.
...
PMID:An in vitro pharmacological examination of venom from the soldierfish Gymnapistes marmoratus. 924 8

We sought to determine the control of ciliary arterial tone by neurogenic acetylcholine (ACh) acting directly on smooth muscle and in conjunction with vasodilator nerves. Isolated posterior ciliary arteries from monkeys responded to ACh (10(-8)-10(-5) M) with dose-related contractions, which were endothelium independent. The response was not affected by cyclooxygenase inhibitors but was abolished by atropine. Relaxations induced at 10(-4) M ACh in the atropine-treated arterial strips were abolished by hexamethonium and NG-nitro-L-arginine (L-NNA), and L-arginine (L-Arg) reversed the response suppressed by L-NNA. Similar results were also obtained on the nicotine (10(-4) M)-induced relaxation. Contractions due to transmural electrical stimulation in the endothelium-denuded strips treated with L-NNA were potentiated by physostigmine and depressed by atropine; the remaining contraction in the presence of atropine was abolished by prazosin. Relaxations associated with electrical stimulation, sensitive to tetrodotoxin, were abolished or reversed to contractions by L-NNA and restored by L-Arg. Stimulation-induced relaxation was attenuated by exogenous ACh and physostigmine and was potentiated by atropine. ACh did not affect the relaxation caused by nitric oxide (NO). Nerve fibers and bundles containing NADPH diaphorase and acetylcholinesterase were histologically demonstrated in the adventitia of ciliary arteries. We conclude that 1) endogenous and exogenous ACh contracts monkey ciliary arteries by acting on muscarinic receptors in smooth muscle cell membranes, 2) vasodilatation elicited by nerve stimulation with electrical pulses or nicotine is mediated by NO synthesized from L-Arg, 3) neurogenic ACh seems to interfere with the nitroxidergic nerve function by acting on prejunctional muscarinic receptors, and 4) high concentrations of ACh stimulate nicotinic receptors in vasodilator nerve terminals and promote the synthesis and/or release of NO.
...
PMID:Cholinergic nerve function in monkey ciliary arteries innervated by nitroxidergic nerve. 961 67

Current treatment approaches in Alzheimer's disease are primarily symptomatic, with the major therapeutic strategy based on acetylcholinesterase inhibition. Alzheimer's disease research should advance over ensuing decade(s) to yield better symptomatic therapies, drugs designed to slow the rate of progression, and disease preventing agents. The next generation of cholinergic agents will include long acting cholinesterase inhibitors with a good safety profile and brain specific muscarinic agonists. The most critical advances in Alzheimer's disease treatment, however, will target slowing of disease progression and prevention of dementia. Therapeutic agents are being developed that interfere with the synthesis, deposition and aggregation of beta-amyloid protein. Clinical trials are presently being conducted with small molecules having nerve growth factor like activity (e.g. AIT-082, cerebrolysin). In addition, estrogen, anti-inflammatory agents (e.g. cyclooxygenase inhibitors) and antioxidant approaches (e.g. vitamin E) are currently being proposed or utilized in disease prevention trials.
...
PMID:Perspectives in clinical Alzheimer's disease research and the development of antidementia drugs. 970 Jun 63

Rats were fed a low-salt (LS; 0.4% NaCl) or high-salt (HS; 4.0% NaCl) diet for 3 days, and the responses of isolated cerebral arteries to acetylcholine (ACh), the nitric oxide (NO)-dependent dilator bradykinin, and the NO donor 6-(2-hydroxy-1-methyl-2-nitrosohydrazino)-N-methyl-1-hex-anamine (NOC-9) were determined. ACh-induced vasodilation and NO release, assessed with the fluorescent NO indicator 4,5-diaminofluorescein (DAF-2) diacetate, were eliminated with the HS diet. Inhibition of cyclooxygenase, cytochrome P-450 epoxygenase, and acetylcholinesterase did not alter ACh responses. Bradykinin and NOC-9 caused a similar dilation in cerebral arteries of all groups. Arteries from animals on LS or HS diets exhibited similar levels of basal superoxide (O(2)(-)) production, assessed by dihydroethidine fluorescence, and ACh responses were unaffected by O(2)(-) scavengers. Muscarinic type 3 receptor expression was unaffected by dietary salt intake. These results indicate that 1) a HS diet attenuates ACh reactivity in cerebral arteries by inhibiting NO release, 2) this attenuation is not due to production of a cyclooxygenase-derived vasoconstrictor or elevated O(2)(-) levels, and 3) alteration(s) in ACh signaling are located upstream from NO synthase.
...
PMID:High-salt diet depresses acetylcholine reactivity proximal to NOS activation in cerebral arteries. 1206 9


1 2 3 Next >>

---