12 results on '"Rowan, Edward G."'
Search Results
2. Protective action of N-acetyl-L-cysteine associated with a polyvalent antivenom on the envenomation induced by Lachesis muta muta (South American bushmaster) in rats.
- Author
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Leão-Torres AG, Pires CV, Ribelato AC, Zerbinatti MC, Santarém CL, Nogueira RMB, Giometti IC, Giuffrida R, Silva EO, Gerez JR, Silva NJ Jr, Rowan EG, and Floriano RS
- Subjects
- Acetylcysteine therapeutic use, Animals, Antivenins therapeutic use, Male, Rats, Rats, Wistar, Viper Venoms toxicity, Crotalid Venoms toxicity, Viperidae
- Abstract
In this study, we examined the potential use of N-acetyl-L-cysteine (NAC) in association with a polyvalent antivenom and as stand-alone therapy to reduce the acute local and systemic effects induced by Lachesis muta muta venom in rats. Male Wistar rats (300-350 g) were exposed to L. m. muta venom (1.5 mg/kg - i.m.) and subsequently treated with anti-Bothrops/Lachesis serum (antivenom:venom ratio 1:3 'v/w' - i.p.) and NAC (150 mg/kg - i.p.) separately or in association; the animals were monitored for 120 min to assess changes in temperature, locomotor activity, local oedema formation and the prevalence of haemorrhaging. After this time, animals were anesthetized in order to collect blood samples through intracardiac puncture and then euthanized for collecting tissue samples; the hematological-biochemical and histopathological analyses were performed through conventional methods. L. m. muta venom produced pronounced local oedema, subcutaneous haemorrhage and myonecrosis, with both antivenom and NAC successfully reducing the extent of the myonecrotic lesion when individually administered; their association also prevented the occurrence of subcutaneous haemorrhage. Venom-induced creatine kinase (CK) release was significantly prevented by NAC alone or in combination with antivenom; NAC alone failed to reduce the release of hepatotoxic (alanine aminotransferase) and nephrotoxic (creatinine) serum biomarkers induced by L. m. muta venom. Venom induced significant increase of leucocytes which was also associated with an increase of neutrophils, eosinophils and monocytes; antivenom and NAC partially reduced these alterations, with NAC alone significantly preventing the increase of eosinophils whereas neither NAC or antivenom prevented the increase in monocytes. Venom did not induce changes in the erythrogram parameters. In the absence of a suitable antivenom, NAC has the potential to reduce a number of local and systemic effects caused by L. m. muta venom., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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- View/download PDF
3. Cardiovascular activity of Micrurus lemniscatus lemniscatus (South American coralsnake) venom.
- Author
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Floriano RS, Torres-Bonilla KA, Rojas-Moscoso JA, Dias L, Rocha T, Silva NJ Jr, Hyslop S, and Rowan EG
- Subjects
- Animals, Hemodynamics, Hypotension chemically induced, Myocardium, Rats, Cardiovascular System drug effects, Coral Snakes, Elapid Venoms toxicity, Heart drug effects
- Abstract
Envenomation by coralsnakes (Micrurus spp.) is characterized by blockade of peripheral neurotransmission mediated by the presence of α- and β-neurotoxins. However, little is known about their cardiovascular activity. Micrurus lemniscatus lemniscatus is a coralsnake found in the Amazon basin and occasionally causes envenomation in humans. In this study, we examined the hemodynamic, vascular and atrial responses to M. l. lemniscatus venom. Anesthetized rats were used for hemodynamic and electrocardiogram (ECG) recordings; in vitro experiments were carried out in rat isolated thoracic aorta and atria preparations. In vivo, venom (0.1 and 0.3 mg/kg) caused immediate and persistent hypotension that was maximal within the first minute with both doses being lethal after ~40 and ~20 min, respectively. ECG, heart and respiratory rates were not altered during the transient hypotension phase induced by venom but all altered prior to death. There was no evidence of myonecrosis in cardiac muscle tissue, pulmonary hemorrhage nor thrombosis in anesthetized rats exposed to venom. In vitro, venom (10 μg/ml) did not contract aortic strips nor affected the maximal responses to pre-contraction with phenylephrine (PE, 0.0001-30 μM) in strips with and without endothelium. However, venom (10 μg/ml) relaxed aortic strips with endothelium pre-contracted with PE. In aortic strips pre-contracted with PE, venom prevented acetylcholine (0.0001-30 μM)-induced relaxation in strips with endothelium without affecting relaxation induced by sodium nitroprusside (0.1-100 nM) in strips without endothelium. Venom (30 μg/ml) produced a transient increase of atrial contractile force without affecting atrial rate. Taken together these findings indicate a predominantly vascular action of the venom, most likely involving toxins interacting with muscarinic receptors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
4. Cytotoxicity of Nubein6.8 peptide isolated from the snake venom of Naja nubiae on melanoma and ovarian carcinoma cell lines.
- Author
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Abdel-Ghani LM, Rahmy TR, Tawfik MM, Kaziri I, Al-Obaidi A, Rowan EG, Plevin R, and Abdel-Rahman MA
- Subjects
- Animals, Antineoplastic Agents pharmacology, Apoptosis drug effects, Cell Line, Cell Line, Tumor, Cell Survival drug effects, Colony-Forming Units Assay, DNA Damage drug effects, Elapid Venoms metabolism, Humans, Naja, Neoplasms drug therapy, Peptides chemistry, Peptides metabolism, Peptides toxicity, Signal Transduction, Antineoplastic Agents chemistry, Elapid Venoms chemistry, Elapid Venoms toxicity
- Abstract
This study was conducted to examine the cytotoxic effects of Nubein6.8 isolated from the venom of the Egyptian Spitting Cobra Naja nubiae on melanoma (A375) and ovarian carcinoma cell lines and to reveal its mode of action. The size of Nubein6.8 (6801.8 Da) and its N-terminal sequence are similar to cytotoxins purified from the venom of other spitting cobras. Nubein6.8 showed a high significant cytotoxic effect on A375 cell line and moderate effect on A2780. A clonogenic assay showed that Nubein6.8 has a significant long-term potency on A375 cell survival when compared to A2780. The molecular intracellular signaling pathways of Nubein6.8 have been investigated using Western blotting analysis, flow cytometry, and microscale protein labeling. This data revealed that Nubein6.8 has DNA damaging effects and the ability to activate apoptosis in both tumor cell lines. Cellular uptake recordings revealed that the labeled-Nubein6.8 was intracellularly present in A375 cells while A2780 displayed resistance against it. SEM examination showed that Nubein6.8 was found to have high accessibility to malignant melanoma cells. The apoptotic effect of Nubein6.8 was confirmed by TEM examination that revealed many evident characteristics for Nubein6.8 apoptotic efficacy on A375 cell sections. Also, TEM reflected many resistant characteristics that faced Nubein6.8 acquisition through ovarian carcinoma cell sections. Accordingly, the snake venom peptide of Nubein6.8 is a promising template for developing potential cytotoxic agents targeting human melanoma and ovarian carcinoma., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
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5. Scorpion venom increases acetylcholine release by prolonging the duration of somatic nerve action potentials.
- Author
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O Collaço RC, Hyslop S, Dorce VAC, Antunes E, and Rowan EG
- Subjects
- Animals, Animals, Newborn, Cells, Cultured, Chickens, Female, Male, Membrane Potentials drug effects, Membrane Potentials physiology, Mice, Mice, Inbred BALB C, Muscle Contraction drug effects, Muscle Contraction physiology, Organ Culture Techniques, Rats, Rats, Wistar, Time Factors, Acetylcholine metabolism, Action Potentials drug effects, Action Potentials physiology, Neuromuscular Junction drug effects, Neuromuscular Junction metabolism, Scorpion Venoms pharmacology
- Abstract
Scorpionism is frequently accompanied by a massive release of catecholamines and acetylcholine from peripheral nerves caused by neurotoxic peptides present in these venoms, which have high specificity and affinity for ion channels. Tityus bahiensis is the second most medically important scorpion species in Brazil but, despite this, its venom remains scarcely studied, especially with regard to its pharmacology on the peripheral (somatic and autonomic) nervous system. Here, we evaluated the activity of T. bahiensis venom on somatic neurotransmission using myographic (chick and mouse neuromuscular preparations), electrophysiological (MEPP, EPP, resting membrane potentials, perineural waveforms, compound action potentials) and calcium imaging (on DRG neurons and muscle fibres) techniques. Our results show that the major toxic effects of T. bahiensis venom on neuromuscular function are presynaptically driven by the increase in evoked and spontaneous neurotransmitter release. Low venom concentrations prolong the axonal action potential, leading to a longer depolarization of the nerve terminals that enhances neurotransmitter release and facilitates nerve-evoked muscle contraction. The venom also stimulates the spontaneous release of neurotransmitters, probably through partial neuronal depolarization that allows calcium influx. Higher venom concentrations block the generation of action potentials and resulting muscle twitches. These effects of the venom were reversed by low concentrations of TTX, indicating voltage-gated sodium channels as the primary target of the venom toxins. These results suggest that the major neuromuscular toxicity of T. bahiensis venom is probably mediated mainly by α- and β-toxins interacting with presynaptic TTX-sensitive ion channels on both axons and nerve terminals., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2019
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6. Individual variability of venom from the European adder (Vipera berus berus) from one locality in Eastern Hungary.
- Author
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Malina T, Krecsák L, Westerström A, Szemán-Nagy G, Gyémánt G, M-Hamvas M, Rowan EG, Harvey AL, Warrell DA, Pál B, Rusznák Z, and Vasas G
- Subjects
- Age Factors, Animals, Chickens, Female, Hungary, Male, Neuromuscular Junction drug effects, Sex Factors, Strontium chemistry, Biological Variation, Population, Neurotoxins chemistry, Neurotoxins toxicity, Phospholipases A2 chemistry, Viper Venoms chemistry, Viper Venoms toxicity, Viperidae
- Abstract
We have revealed intra-population variability among venom samples from several individual European adders (Vipera berus berus) within a defined population in Eastern Hungary. Individual differences in venom pattern were noticed, both gender-specific and age-related, by one-dimensional electrophoresis. Gelatin zymography demonstrated that these individual venoms have different degradation profiles indicating varying protease activity in the specimens from adders of different ages and genders. Some specimens shared a conserved region of substrate degradation, while others had lower or extremely low protease activity. Phospholipase A
2 activity of venoms was similar but not identical. Interspecimen diversity of the venom phospholipase A2 -spectra (based on the components' molecular masses) was detected by MALDI-TOF MS. The lethal toxicity of venoms (LD50 ) also showed differences among individual snakes. Extracted venom samples had varying neuromuscular paralysing effect on chick biventer cervicis nerve-muscle preparations. The paralysing effect of venom was lost when calcium in the physiological salt solution was replaced by strontium; indicating that the block of twitch responses to nerve stimulation is associated with the activity of a phospholipase-dependent neurotoxin. In contrast to the studied V. b. berus venoms from different geographical regions so far, this is the first V. b. berus population discovered to have predominantly neurotoxic neuromuscular activity. The relevance of varying venom yields is also discussed. This study demonstrates that individual venom variation among V. b. berus living in particular area of Eastern Hungary might contribute to a wider range of clinical manifestations of V. b. berus envenoming than elsewhere in Europe., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2017
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7. The neuromuscular activity of Bothriopsis bilineata smaragdina (forest viper) venom and its toxin Bbil-TX (Asp49 phospholipase A2) on isolated mouse nerve-muscle preparations.
- Author
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Floriano RS, Rocha T, Carregari VC, Marangoni S, da Cruz-Höfling MA, Hyslop S, Rodrigues-Simioni L, and Rowan EG
- Subjects
- Analysis of Variance, Animals, Immunohistochemistry, Male, Mice, Mice, Inbred BALB C, Muscle Contraction drug effects, Muscle, Skeletal drug effects, Phrenic Nerve drug effects, Neuromuscular Junction drug effects, Phospholipases A2 toxicity, Viper Venoms toxicity, Viperidae metabolism
- Abstract
The presynaptic action of Bothriopsis bilineata smaragdina (forest viper) venom and Bbil-TX, an Asp49 PLA2 from this venom, was examined in detail in mouse phrenic nerve-muscle (PND) preparations in vitro and in a neuroblastoma cell line (SK-N-SH) in order to gain a better insight into the mechanism of action of the venom and associated Asp49 PLA2. In low Ca(2+) solution, venom (3μg/ml) caused a quadriphasic response in PND twitch height whilst at 10μg/ml the venom additionally induced an abrupt and marked initial contracture followed by neuromuscular facilitation, rhythmic oscillations of nerve-evoked twitches, alterations in baseline and progressive blockade. The venom slowed the relaxation phase of muscle twitches. In low Ca(2+), Bbil-TX [210nM (3μg/ml)] caused a progressive increase in PND twitch amplitude but no change in the decay time constant. Venom (10μg/ml) and Bbil-TX (210nM) caused minor changes in the compound action potential (CAP) amplitude recorded from sciatic nerve preparations, with no significant effect on rise time and latency; tetrodotoxin (3.1nM) blocked the CAP at the end of the experiments. In mouse triangularis sterni nerve-muscle (TSn-m) preparations, venom (10μg/ml) and Bbil-TX (210nM) significantly reduced the perineural waveform associated with the outward K(+) current while the amplitude of the inward Na(+) current was not significantly affected. Bbil-TX (210nM) caused a progressive increase in the quantal content of TSn-m preparations maintained in low Ca(2+) solution. Venom (3μg/ml) and toxin (210nM) increased the calcium fluorescence in SK-N-SH neuroblastoma cells loaded with Fluo3 AM and maintained in low or normal Ca(2+) solution. In normal Ca(2+), the increase in fluorescence amplitude was accompanied by irregular and frequent calcium transients. In TSn-m preparations loaded with Fluo4 AM, venom (10μg/ml) caused an immediate increase in intracellular Ca(2+) followed by oscillations in fluorescence and muscle contracture; Bbil-TX did not change the calcium fluorescence in TSn-m preparations. Immunohistochemical analysis of toxin-treated PND preparations revealed labeling of junctional ACh receptors but a loss of the presynaptic proteins synaptophysin and SNAP25. Together, these data confirm the presynaptic action of Bbil-TX and show that it involves modulation of K(+) channel activity and presynaptic protein expression., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
- Full Text
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8. The effect of temperature on the effects of the phospholipase A₂ neurotoxins β-bungarotoxin and taipoxin at the neuromuscular junction.
- Author
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Fathi B, Harvey AL, and Rowan EG
- Subjects
- Animals, Male, Mice, Mice, Inbred BALB C, Neuromuscular Junction metabolism, Phospholipase A2 Inhibitors toxicity, Bungarotoxins toxicity, Elapid Venoms toxicity, Neuromuscular Junction drug effects, Neurotoxins toxicity, Temperature
- Abstract
Snake venom neurotoxins with phospholipase A₂ affect the neuromuscular junction with three distinct phases. There is a transient decrease in twitch height, followed by a facilitatory phase and finally a progressive blockade. It has been suggested that the initial phase is a direct consequence of the binding of the toxins to nerve terminals. This study was designed to determine whether the initial phase is present under conditions that would reduce the enzyme activity of the toxins. At 27 °C, β-bungarotoxin and taipoxin exhibited all three phases, i.e. 5-6 min after exposure to the preparation, twitch height was significantly reduced (P < 0.5) to 50 ± 4% and 64 ± 9% of control respectively. This was followed by facilitation and subsequent blockade. However, at 20 °C, neither toxin exhibited the first phase while the second phase, although reduced, clearly occurred and the blocking activity of these toxins always appeared. The data clearly demonstrate that the initial fall is temperature dependent as reducing the temperature from 27 °C to 20 °C blocks the first phase. As the second phase still occurs the toxins must have bound to their target. Therefore, the first phase cannot simply be a toxin binding step., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
- Full Text
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9. Classic toxins.
- Author
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Rowan EG
- Subjects
- Toxicology
- Published
- 2011
- Full Text
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10. The neuromuscular activity of paradoxin: a presynaptic neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus).
- Author
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Hodgson WC, Dal Belo CA, and Rowan EG
- Subjects
- Animals, Cells, Cultured, Chickens, Diaphragm drug effects, Electrophysiology, Extracellular Space drug effects, Extracellular Space metabolism, Fibroblasts drug effects, In Vitro Techniques, Male, Membrane Potentials drug effects, Mice, Muscle Contraction drug effects, Muscle, Skeletal cytology, Muscle, Skeletal drug effects, Patch-Clamp Techniques, Phospholipases A metabolism, Phrenic Nerve drug effects, Strontium, Elapid Venoms toxicity, Neurotoxins toxicity, Receptors, Presynaptic drug effects, Snakes physiology
- Abstract
The inland taipan is the world's most venomous snake. However, little is known about the neuromuscular activity of the venom or paradoxin (PDX), a presynaptic neurotoxin from the venom. Venom (10microg/ml) and PDX (65nM) abolished indirect twitches of the chick biventer cervicis and mouse phrenic nerve diaphragm preparations. The time to 90% inhibition by PDX was significantly increased by replacing Ca(2+) (2.5mM) in the physiological solution with Sr(2+) (10mM). In the biventer cervicis muscle, venom (10microg/ml), but not PDX (65nM), significantly inhibited responses to ACh (1mM) and carbachol (20microM), but not KCl (40mM). In the mouse diaphragm (low Ca(2+); room temperature), the inhibitory effect of PDX (6.5nM) was delayed and a transient increase (746+/-64%; n=5) of contractions observed. In intracellular recording experiments using the mouse hemidiaphragm, PDX (6.5-65nM) significantly increased quantal content and miniature endplate potential frequency prior to blocking evoked release of acetylcholine. In extracellular recording experiments using the mouse triangularis sterni, PDX (2.2-65nM) significantly inhibited the voltage-dependent K(+), but not Na(+), waveform. In patch clamp experiments using B82 mouse fibroblasts stably transfected with rKv 1.2, PDX (22nM; n=3) had no significant effect on currents evoked by 10mV step depolarisations from -60 to +20mV. PDX exhibits all the pharmacology associated with beta-neurotoxins, and appears to be one of the most potent, if not the most potent beta-neurotoxin yet discovered.
- Published
- 2007
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11. Pharmacological and structural characterization of a novel phospholipase A2 from Micrurus dumerilii carinicauda venom.
- Author
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Belo CA, Leite GB, Toyama MH, Marangoni S, Corrado AP, Fontana MD, Southan A, Rowan EG, Hyslop S, and Rodrigues-Simioni L
- Subjects
- Amino Acid Sequence, Animals, Chickens, Diaphragm innervation, Elapid Venoms pharmacology, Male, Mice, Molecular Sequence Data, Phospholipases A toxicity, Phospholipases A2, Phrenic Nerve drug effects, Phrenic Nerve physiology, Sequence Homology, Amino Acid, Elapid Venoms enzymology, Elapidae, Phospholipases A chemistry, Phospholipases A pharmacology
- Abstract
We have isolated a new phospholipase A2 (MiDCA1) from the venom of the coral snake Micrurus dumerilii carinicauda. This toxin, which had a molecular mass of 15,552Da, shared high sequence homology with the PLA2 toxins MICNI A and B from Micrurus nigrocinctus venom (77.7% and 73.1%, respectively). In chick biventer cervicis preparations, MiDCA1 produced concentration- and time-dependent neuromuscular blockade that reached 100% after 120 min (2.4 microM, n = 6); contractures to exogenously applied carbachol (8 microM) and KCl (13 mM) were still seen after complete blockade. In mouse phrenic-nerve diaphragm preparations, MiDCA1 (2.4 microM; n = 6) caused triphasic changes followed by partial neuromuscular blockade. Intracellular recordings of end-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) from mouse diaphragm preparations showed that MiDCA1 increased the quantal content by 386+/-12% after 10 min (n = 14; p<0.05) and caused a triphasic change in the frequency of MEPPs. MiDCA1 also decreased the resting membrane potential, an effect that was prevented by tetrodotoxin and/or low extracellular calcium, but not by d-tubocurarine. The toxin increased the amplitude of mouse sciatic-nerve compound action potentials by 30+/-9% (0.6 microM; p<0.05). Potassium currents elicited in freshly dissociated dorsal root ganglia neurones were blocked by 31+/-1% (n = 4; p<0.05) in the presence of 2.4 microM MiDCA1. These results show that MiDCA1 is a new presynaptic phospholipase A2 that produces neuromuscular blockade in vertebrate nerve-muscle preparations. The triphasic effects seen in mammalian preparations and the facilitatory response were probably caused mainly by the activation of sodium channels, complemented by the blockade of nerve terminal potassium channels. The inability of d-turocurarine to prevent the depolarization by MiDCA1 indicated that cholinergic nicotinic receptors were not involved in this phenomenon.
- Published
- 2005
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12. Effects of muscarinic toxins MT2 and MT7, from green mamba venom, on m1, m3 and m5 muscarinic receptors expressed in Chinese Hamster Ovary cells.
- Author
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Bradley KN, Rowan EG, and Harvey AL
- Subjects
- Animals, CHO Cells drug effects, CHO Cells metabolism, Calcium metabolism, Carbachol metabolism, Carbachol pharmacology, Cricetinae, Cricetulus, Cytosol drug effects, Cytosol metabolism, Dose-Response Relationship, Drug, Elapid Venoms pharmacology, Elapidae physiology, Fura-2 metabolism, Humans, Muscarinic Agonists pharmacology, Muscarinic Antagonists metabolism, Muscarinic Antagonists pharmacology, Neurotoxins pharmacology, Radioligand Assay, Receptors, Muscarinic drug effects, Receptors, Muscarinic genetics, Reptilian Proteins, Transfection, Elapid Venoms metabolism, Muscarinic Agonists metabolism, Neurotoxins metabolism, Receptors, Muscarinic metabolism
- Abstract
Several small proteins called muscarinic toxins (MTs) have been isolated from venom of green mamba (Dendroaspis angusticeps). They have previously been shown in radioligand binding studies to have high selectivity and affinity for individual muscarinic receptor subtypes, but less is known of their functional effects. This study has examined the actions of two of these MTs, MT2 and MT7, using changes in cytosolic Ca(2+) ([Ca(2+)](i)) measured using the fluorescent indicator fura-2 in Chinese Hamster Ovary (CHO) cells stably transfected with individual muscarinic receptor subtypes, m1, m3 and m5. MT2 activated the m1 receptor: at concentrations above 100 nM it caused significant and concentration-dependent increases in [Ca(2+)](i). From 25 to 800 nM MT2 also produced increases in [Ca(2+)](i) by activating m3 receptors, although these increases in [Ca(2+)](i) were not strictly concentration-dependent with only intermittent responses being recorded (i.e. it was not always possible to obtain a response to the agonist with each application of the compound). MT2 (800-1600 nM) also caused significant increases in [Ca(2+)](i) in CHO cells expressing the m5 muscarinic receptor subtype. MT7 (1 microM) displayed no agonist activity at any of the muscarinic receptors but was a potent non-competitive antagonist (at 20 nM) at the m1 muscarinic receptor subtype. It had no antagonist activity at the m3 or m5 subtypes. These results indicate that MT7 is a highly specific antagonist at the m1 muscarinic receptor subtype as suggested by results from radioligand binding studies. However, MT2 is less selective for the m1 muscarinic receptor than previously described as it also exhibits agonist activity at the m3 and m5 muscarinic receptors, which was not detected in radioligand binding studies.
- Published
- 2003
- Full Text
- View/download PDF
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