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Urology Jul 1977Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic... (Review)
Review
Various parasympathomimetic drugs are discussed, including the choline esters, bethanechol, carbachol, methacholine chloride, and furtrethonium. Other cholinomimetic agents include muscarine, muscarone, arecholine, and pilocarpine. Anticholinesterase agents inhibit or inactivate acetylcholinesterase enzyme and thus result in a prolonged stimulation of cholinergic receptors by endogenous ACh. Bethanechol is the most widely used parasympathomimetic drug in the United States. Its action is mainly muscarinic with activity largely confined to the urinary bladder and to a lesser degree the gastrointestinal tract. It can be administered only subcutaneously or orally, and adequate dosage is necessary for a successful response.
Topics: Animals; Bethanechol Compounds; Carbachol; Cholinesterase Inhibitors; Humans; Male; Methacholine Compounds; Muscarine; Muscle, Smooth; Neostigmine; Parasympathomimetics; Phenoxybenzamine; Physostigmine; Pyridinium Compounds; Quaternary Ammonium Compounds; Urethra; Urinary Bladder
PubMed: 17940
DOI: 10.1016/0090-4295(77)90052-8 -
European Journal of Pharmacology Apr 1989The dose-response curve for the muscarine-induced depolarisation of the rat isolated superior cervical ganglion, studied over the concentration range of 3 nM-1 mM, was...
The dose-response curve for the muscarine-induced depolarisation of the rat isolated superior cervical ganglion, studied over the concentration range of 3 nM-1 mM, was biphasic. An apparent maximum was obtained at around 1-3 microM muscarine, but this was only a plateau between the two parts of the curve. Two cardioselective antagonists, gallamine (10 microM) and AF-DX 116 (1 microM) had a complex action on this dose-response curve. The dose-response curve between 0.01 and 0.3 microM was shifted to the right, the responses around 3 microM muscarine were enhanced, but the dose-response curve over 30 microM muscarine was unaffected. The M1-selective antagonist pirenzepine (0.05 microM) depressed all parts of the dose-response curve, but it still appeared biphasic. Pretreatment of the ganglion with pertussis toxin (1 microgram/ml) enhanced the depolarisation to muscarine 0.01-1000 microM and the dose-response curve became less biphasic. Like gallamine and AF-DX 116, pertussis toxin abolished the muscarinic M2-mediated hyperpolarisation of the ganglion recorded in 0.3 microM pirenzepine. It is concluded that the presence of an underlying M2-mediated hyperpolarisation contributes to the biphasic nature of the dose-response curve to muscarine.
Topics: Animals; Dose-Response Relationship, Drug; Gallamine Triethiodide; Ganglia, Spinal; In Vitro Techniques; Muscarine; Pertussis Toxin; Pirenzepine; Rats; Virulence Factors, Bordetella
PubMed: 2721572
DOI: 10.1016/0014-2999(89)90192-1 -
Neuropharmacology Mar 1995The effects of muscarine on whole-cell Ca2+ channel currents in SH-SY5Y cells were studied using conventional and perforated-patch-clamp techniques, with 10 mM Ba2+ as...
The effects of muscarine on whole-cell Ca2+ channel currents in SH-SY5Y cells were studied using conventional and perforated-patch-clamp techniques, with 10 mM Ba2+ as charge carrier. Muscarine (10-300 microM) caused concentration-dependent inhibitions of Ca2+ channel currents which were only reversible when perforated-patch recordings were used. Inhibition of currents was associated with slowing of activation kinetics in approximately 50% of cells. In the presence of 5 microM nifedipine, muscarine was still able to inhibit currents, but after pre-exposure of cells to 1 microM omega-conotoxin GVIA the inhibitory effects of muscarine were almost completely lost. In the presence of 100 microM muscarine, Bay K 8644 (5 microM) was still able to enhance current amplitudes. Pre-treatment of cells with pertussis toxin (250 ng/ml for 16-24 hr) or inclusion of 1 mM GDP-beta-S in the patch-pipette prevented the inhibitory actions of muscarine. Hexahydrosiladifenidol (0.1-1 microM) antagonized the actions of muscarine (calculated pA2 7.1) but the presence of 10 microM pirenzipine or 0.1 microM methoctramine in the bath solution did not alter the degree of current inhibition caused by 100 microM muscarine. In summary, these results indicate that muscarine in SH-SY5Y cells causes inhibition of N-type Ca2+ channels via a M3 receptor coupled to a pertussis toxin-sensitive G-protein.
Topics: Brain Neoplasms; Calcium Channel Blockers; GTP-Binding Proteins; Humans; Muscarine; Muscarinic Agonists; Neuroblastoma; Parasympatholytics; Patch-Clamp Techniques; Pertussis Toxin; Piperidines; Receptors, Muscarinic; Tumor Cells, Cultured; Virulence Factors, Bordetella
PubMed: 7630487
DOI: 10.1016/0028-3908(94)00161-k -
Neuroscience Research Nov 1996Muscarine and somatostatin enhance an inward rectifier K+ conductance in the AtT-20 pituitary cell line. Both effects are abolished by pertussis toxin (PTX). To... (Comparative Study)
Comparative Study
Muscarine and somatostatin enhance an inward rectifier K+ conductance in the AtT-20 pituitary cell line. Both effects are abolished by pertussis toxin (PTX). To determine which PTX-sensitive G protein mediates these agonist effects, we made cDNAs encoding mutant PTX-insensitive Gi alpha subtypes, in which the cysteine residue fourth from the C terminus was replaced with serine. The mutated cDNA was transfected into AtT-20 cells, resulting in stable cell lines overexpressing a Gi alpha subtype. As controls, wild-type Gi alpha cDNA was transfected into AtT-20 cells. The agonist-induced increase of the inward rectifier K+ conductance in the transfectants was examined with the whole-cell clamp method. Only in the cell lines into which the mutated (PTX-insensitive) Gi2 alpha cDNA was transfected, did the muscarine response become PTX-insensitive, suggesting that Gi2 couples to the muscarinic receptor and enhances the activity of the inward rectifier K+ channel. However, PTX-insensitive somatostatin responses were not obtained in any of the cell lines transfected with a mutated Gi alpha cDNA, suggesting either that none of the Gi subtypes is a transducer for the somatostatin effect or that the mutation prevents the coupling of the Gi alpha to the somatostatin receptor.
Topics: Animals; Cell Line; DNA, Complementary; GTP-Binding Proteins; Mice; Muscarine; Muscarinic Agonists; Mutagenesis, Site-Directed; Patch-Clamp Techniques; Pertussis Toxin; Pituitary Gland; Potassium Channels; Somatostatin; Transfection; Virulence Factors, Bordetella
PubMed: 9121737
DOI: 10.1016/s0168-0102(96)01111-x -
British Journal of Pharmacology Jan 1985The adrenaline-induced hyperpolarization (AdH) and the responses evoked by muscarine and luteinizing hormone releasing hormone (LHRH) were recorded from neurones in...
The adrenaline-induced hyperpolarization (AdH) and the responses evoked by muscarine and luteinizing hormone releasing hormone (LHRH) were recorded from neurones in amphibian sympathetic ganglia by means of the sucrose gap technique. The amplitude of the AdH was reduced when 'M-channel' closure was promoted by superfusion of LHRH or muscarine. 4-Aminopyridine (4-AP, 1 mM) antagonized the AdH, but not the depolarization evoked by muscarinic agonists. This implies that the channels involved in the electrogenesis of the AdH have different pharmacological properties from 'M-channels' and that the AdH is not generated by the opening of 'M-channels' outside their normal voltage range. Possible explanations for the attenuation of the AdH by muscarine and LHRH might be that (i) intracellular biochemical changes produced by these substances somehow interfere with the generation of the AdH or that (ii) muscarine and LHRH have allosteric interactions with the adrenoceptor mediating the AdH.
Topics: 4-Aminopyridine; Aminopyridines; Animals; Electrophysiology; Epinephrine; Ganglia, Sympathetic; Gonadotropin-Releasing Hormone; In Vitro Techniques; Muscarine; Rana catesbeiana
PubMed: 2983802
DOI: No ID Found -
Brain Research Sep 1998Cholinergic mechanisms in the septohippocampal pathway contribute to several cognitive functions and impaired cholinergic transmission in this pathway may be related to...
Cholinergic mechanisms in the septohippocampal pathway contribute to several cognitive functions and impaired cholinergic transmission in this pathway may be related to the memory loss and dementia that accompanies normal aging and Alzheimer's disease and behavioral studies suggest that muscarinic mechanisms in the medial septum/diagonal band of Broca (MSDB) may contribute to these functions. The goal of the present study was to begin a characterization of the physiological and pharmacological effects of muscarine on antidromically identified septohippocampal neurons (SHNs). Muscarinic agonists produced a concentration-dependent excitation in >90% of SHNs tested using extracellular recordings in an in vitro rat brain slice preparation. The SHNs excited by muscarine had a broad range of conduction velocities (0.2 to 3.7 m/s; mean: 1.6+/-0.06 m/s; n=110), suggesting involvement of neurons with both slow (possibly cholinergic) and fast (possibly GABAergic) conducting fibers. The muscarine-induced excitations in SHNs were found not to be mediated via M1, M2 or M4 receptors, as they were not blocked by the M1-selective antagonists, pirenzepine or telenzepine or by the M2/M4-selective antagonist, methoctramine. In contrast, the M3-selective antagonist, 4-DAMP-mustard, blocked muscarinic excitations in a majority of SHNs, indicating the presence of M3 as well as non-M3-type responses. McN-A-343, an M1 and M5-selective agonist, excited 33% of neurons tested, confirming involvement of non-M3 receptors (possibly M5) and M3 receptors. Since the cholinergic and GABAergic MSDB neurons together innervate almost every type of hippocampal neuron, the effects of muscarine on SHNs would also have a profound effect on hippocampal circuitry.
Topics: Animals; Drug Administration Schedule; Electrophysiology; Frontal Lobe; Hippocampus; In Vitro Techniques; Male; Muscarine; Neurons; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Septum Pellucidum
PubMed: 9733970
DOI: 10.1016/s0006-8993(98)00729-x -
The European Journal of Neuroscience Jul 1999Li+ is known to facilitate the onset of status epilepticus induced by cholinergic stimulation, although the underlying mechanisms are not clear. Under whole-cell current...
Li+ is known to facilitate the onset of status epilepticus induced by cholinergic stimulation, although the underlying mechanisms are not clear. Under whole-cell current clamp conditions with a CsCl-based internal solution, cortical pyramidal cells display a single plateau-spike followed by a slow depolarizing afterpotential (DAP) in response to injection of a short current pulse. However, the same current pulse generated a burst of plateau-spikes after application of Li+ (2 mM) and muscarine (10 microM). As similar bursts of plateau-spikes were generated through an enhancement of the slow DAP when [K+]o was raised (Kang et al. 1998), we have investigated the effects of Li+ and muscarine on the Ca2+-dependent cationic current underlying the slow DAP, measured as the slow tail current evoked after the offset of depolarizing voltage pulses. Muscarine enhanced the amplitudes of both early and late components of the slow tail current. This effect of muscarine was markedly potentiated by Li+, while Li+ by itself affected the slow tail current only slightly. Intracellular application of heparin (0.5-1 mg/mL) suppressed the effect of muscarine in the presence of Li+. These results suggest that inositol-trisphosphate-induced Ca2+ release is involved in the cooperative enhancement of the slow tail current, and this cooperation may be one of the mechanisms underlying facilitation of the onset of epilepsy induced by these agents.
Topics: Animals; Cations; Cerebral Cortex; Drug Synergism; Electric Conductivity; Heparin; In Vitro Techniques; Lithium; Muscarine; Pyramidal Cells; Rats; Rats, Sprague-Dawley
PubMed: 10383629
DOI: 10.1046/j.1460-9568.1999.00657.x -
The American Journal of Physiology Jul 1996Coexpression in Xenopus oocytes of the cloned cardiac inward rectifier subunits Kir 3.1 and Kir 3.4 results in G protein-stimulated channel activity closely resembling...
Coexpression in Xenopus oocytes of the cloned cardiac inward rectifier subunits Kir 3.1 and Kir 3.4 results in G protein-stimulated channel activity closely resembling the muscarinic channel underlying the inwardly rectifying K+ current in atrial myocytes. To determine the stoichiometry and relative subunit positions within the channel, Kir 3.1 and Kir 3.4 were coexpressed in varying ratios with cloned G beta 1 gamma 2 subunits and also as tandemly linked tetramers with different relative subunit positions. The results reveal that the most efficient channel comprises two subunits of each type in an alternating array within the tetramer. To localize regions important for subunit coassembly and G protein sensitivity, chimeric subunits containing domains from either Kir 3.1, Kir 3.4, or the G protein-insensitive subunit Kir 4.1 were expressed. The results demonstrate that the transmembrane domains dictate the potentiation of the coassembled channels and that, although the NH4- or COOH-termini of both subunits alone can confer G protein sensitivity, both termini are required for maximal stimulation by G beta 1 gamma 2.
Topics: Animals; Cloning, Molecular; GTP-Binding Proteins; Intracellular Membranes; Ion Channel Gating; Mathematics; Muscarine; Potassium Channels; Xenopus laevis
PubMed: 8760196
DOI: 10.1152/ajpheart.1996.271.1.H379 -
Naunyn-Schmiedeberg's Archives of... Jan 1985Longitudinal muscle strips of the guinea-pig ileum were incubated with [3H]choline and the effects of muscarinic agonists on smooth muscle contraction and on spontaneous...
Longitudinal muscle strips of the guinea-pig ileum were incubated with [3H]choline and the effects of muscarinic agonists on smooth muscle contraction and on spontaneous and electrically-evoked outflow of tritium were studied. Muscarine and pilocarpine concentration-dependently increased both muscle contraction and spontaneous outflow of [3H]ACh, and inhibited the electrically-evoked outflow of [3H]ACh. The increase in spontaneous outflow was prevented by tetrodotoxin and scopolamine, but not by hexamethonium. Oxotremorine (1-100 microM) did not increase the spontaneous outflow of tritium. Pirenzepine in concentrations of 10 and 100 nM hardly affected the muscle contractions induced by pilocarpine, but significantly antagonized the pilocarpine-evoked increases in [3H]ACh outflow. Likewise, pirenzepine (100 nM) antagonized more effectively the enhancement by muscarine of spontaneous outflow than the inhibitory effect of muscarine on the electrically-evoked release of [3H]ACh. Scopolamine (1 and 10 nM) antagonized to a similar extent the effects of pilocarpine on spontaneous outflow of [3H]ACh and on muscle contraction. The results suggest that the cholinergic nerves of the myenteric plexus are endowed with excitatory (ganglionic) and inhibitory (prejunctional) muscarine receptors which modulate the release of ACh and which differ in their affinities to pirenzepine.
Topics: Acetylcholine; Animals; Benzodiazepinones; Guinea Pigs; Ileum; In Vitro Techniques; Muscarine; Muscle Contraction; Myenteric Plexus; Oxotremorine; Pilocarpine; Pirenzepine; Receptors, Muscarinic; Scopolamine
PubMed: 3838575
DOI: 10.1007/BF00515558 -
Journal of Pharmaceutical Sciences Sep 1962
Topics: Agaricales; Chromatography; Muscarine; Parasympathomimetics
PubMed: 13873674
DOI: 10.1002/jps.2600510908