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Experientia Jun 1988Increased muscarinic sensitivity has been associated with altered hormonal states (hypothyroidism and hyperadrenocorticism), chronic administration of muscarinic... (Review)
Review
Increased muscarinic sensitivity has been associated with altered hormonal states (hypothyroidism and hyperadrenocorticism), chronic administration of muscarinic antagonists or antidepressants with muscarinic actions, selective breeding for anticholinesterase sensitivity, and certain inbred strains of rats and mice. Thus, both genetic and environmental factors may influence muscarinic receptor sensitivity. The reasonably detailed studies on the selectively-bred rats have revealed that the Flinders Sensitive Line (FSL) rats weigh less, are less active, are more sensitive to muscarinic agonists and to stressors, and have higher concentrations of hippocampal and striatal muscarinic receptors than 'normal', or the selectively-bred, Flinders Resistant Line (FRL) rats. Thus, there are a number of parallels between FSL rats and depressed humans. The FSL rats may be the first animal model of depression to mimic the actual trait of depression, and not just the state.
Topics: Acetylcholine; Animals; Depression; Disease Models, Animal; Drug Resistance; Humans; Mice; Mice, Inbred Strains; Mood Disorders; Muscarine; Rats; Rats, Inbred Strains; Receptors, Muscarinic
PubMed: 3288493
DOI: 10.1007/BF01958920 -
ELife Jun 2019Olfactory associative learning in is mediated by synaptic plasticity between the Kenyon cells of the mushroom body and their output neurons. Both Kenyon cells and their...
Olfactory associative learning in is mediated by synaptic plasticity between the Kenyon cells of the mushroom body and their output neurons. Both Kenyon cells and their inputs from projection neurons are cholinergic, yet little is known about the physiological function of muscarinic acetylcholine receptors in learning in adult flies. Here, we show that aversive olfactory learning in adult flies requires type A muscarinic acetylcholine receptors (mAChR-A), particularly in the gamma subtype of Kenyon cells. mAChR-A inhibits odor responses and is localized in Kenyon cell dendrites. Moreover, mAChR-A knockdown impairs the learning-associated depression of odor responses in a mushroom body output neuron. Our results suggest that mAChR-A function in Kenyon cell dendrites is required for synaptic plasticity between Kenyon cells and their output neurons.
Topics: Aging; Animals; Behavior, Animal; Drosophila Proteins; Drosophila melanogaster; Learning; Muscarine; Muscarinic Agonists; Mushroom Bodies; Mutation; Odorants; Receptors, Muscarinic; Smell
PubMed: 31215865
DOI: 10.7554/eLife.48264 -
Neuroscience Letters Mar 1987C cells of bullfrog sympathetic ganglia have an M-current similar to that of the larger B cells. However, the M-current of C cells is much less sensitive to muscarinic...
C cells of bullfrog sympathetic ganglia have an M-current similar to that of the larger B cells. However, the M-current of C cells is much less sensitive to muscarinic agonists. The M-current of C cells is blocked by barium and by LHRH (mammalian luteinizing hormone-releasing hormone). LHRH sometimes also decreases a different conductance, with an extrapolated reversal potential near 0 mV. These results demonstrate that the coupling of receptors to ion channels can vary between cell types, even within a single ganglion.
Topics: Animals; Ganglia, Sympathetic; Gonadotropin-Releasing Hormone; Ion Channels; Kinetics; Muscarine; Potassium; Rana catesbeiana; Receptors, Muscarinic
PubMed: 2436111
DOI: 10.1016/0304-3940(87)90315-6 -
Experientia Apr 1957
Topics: Muscarine; Parasympathomimetics; Stereoisomerism
PubMed: 13447893
DOI: 10.1007/BF02158130 -
Fundamental & Clinical Pharmacology 1997The effects of NKH477, a water-soluble forskolin derivative, and dibutyryl-cyclic adenosine monophosphate (dbcAMP) on the release of adrenal catecholamines (CAs) in...
Effects of NKH477, a forskolin derivative, and dibutyryl-cyclic AMP on adrenal catecholamine release in response to splanchnic nerve stimulation, acetylcholine, DMPP and muscarine in anesthetized dogs.
The effects of NKH477, a water-soluble forskolin derivative, and dibutyryl-cyclic adenosine monophosphate (dbcAMP) on the release of adrenal catecholamines (CAs) in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), the nicotinic receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP) and muscarine were examined in anesthetized dogs. NKH477, dbcAMP and the cholinergic agonists were infused and injected, respectively, into the adrenal gland intra-arterially. SNS (3 Hz) or injections of ACh (3 micrograms), DMPP (2 micrograms) and muscarine (2 micrograms) produced increases in CA output determined from adrenal venous blood. Both NKH477 infusion (0.3, 1 and 3 micrograms/min) and dbcAMP infusion (0.1, 0.3 and 1 mg/min) caused dose-dependent enhancement of the SNS-, ACh- and DMPP-induced increases in CA output, whereas they failed to affect the muscarine-induced increases in CA output. Neither NKH477 nor dbcAMP affected basal CA output. Cyclic AMP (cAMP) overflow determined from adrenal venous blood increased during NKH477 infusion. These results indicate that NKH477 and dbcAMP have facilitatory effects on adrenal CA release mediated by nicotinic receptors, but not by muscarinic receptors in the dog, and suggest the selective action of cAMP on nicotinic mechanism.
Topics: Acetylcholine; Adrenal Glands; Animals; Bucladesine; Catecholamines; Colforsin; Dimethylphenylpiperazinium Iodide; Dogs; Female; Infusions, Intra-Arterial; Injections, Intra-Arterial; Male; Muscarine; Muscarinic Agonists; Receptors, Nicotinic; Splanchnic Nerves; Vasodilator Agents
PubMed: 9444518
DOI: 10.1111/j.1472-8206.1997.tb00855.x -
Actualites Pharmacologiques 1977
Topics: Animals; Atropine; Humans; Muscarine; Receptors, Cholinergic; Receptors, Muscarinic; Receptors, Nicotinic; Scopolamine
PubMed: 868615
DOI: No ID Found -
American Journal of Physiology. Lung... May 2023It has been shown that muscarinic acetylcholine receptors (mAChRs) located within the caudal nucleus tractus solitarii (cNTS) mediate a cholinergic inhibitory control...
It has been shown that muscarinic acetylcholine receptors (mAChRs) located within the caudal nucleus tractus solitarii (cNTS) mediate a cholinergic inhibitory control mechanism of the cough reflex. Thus, identification of the involved mAChR subtypes could be of considerable interest for novel therapeutic strategies. In pentobarbital sodium-anesthetized, spontaneously breathing rabbits we investigated the contribution of different mAChR subtypes in the modulation of mechanically and chemically induced cough reflex. Bilateral microinjections of 1 mM muscarine into the cNTS increased respiratory frequency and decreased expiratory activity even to complete suppression. Interestingly, muscarine induced strong cough-suppressant effects up to the complete abolition of the reflex. Microinjections of specific mAChR subtype antagonists (M-M) into the cNTS were performed. Only microinjections of the M antagonist tropicamide (1 mM) prevented muscarine-induced changes in both respiratory activity and cough reflex. The results are discussed in light of the notion that cough involves the activation of the nociceptive system. They also suggest that M receptor agonists may have an important role in cough downregulation within the cNTS.
Topics: Animals; Rabbits; Solitary Nucleus; Acetylcholine; Cough; Muscarine; Receptors, Muscarinic; Reflex; Muscarinic Antagonists
PubMed: 36976922
DOI: 10.1152/ajplung.00325.2022 -
Farmaco (Societa Chimica Italiana :... Aug 2000Novel derivatives of natural muscarine and allo-muscarine, i.e. the benzyl ethers (-)-10 and (-)-12 and the benzoate (-)-13, were synthesized in very high enantiomeric...
Novel derivatives of natural muscarine and allo-muscarine, i.e. the benzyl ethers (-)-10 and (-)-12 and the benzoate (-)-13, were synthesized in very high enantiomeric excess. Target compounds were tested in vitro on guinea pig tissues, and their muscarinic potency was evaluated at M2 (heart force and rate) and M3 (ileum and bladder) receptor subtypes. The derivatives under study were also assayed in vivo on pithed rat. In addition, muscarinic receptor heterogeneity was investigated by determining the affinity and the relative efficacy of compounds (-)-10, (-)-12 and (-)-13 at M2 (heart force and rate) and M3 (ileum and bladder) receptor subtypes.
Topics: Animals; Guinea Pigs; In Vitro Techniques; Magnetic Resonance Spectroscopy; Male; Muscarine; Muscle Contraction; Rats; Receptors, Muscarinic; Stereoisomerism
PubMed: 11132731
DOI: 10.1016/s0014-827x(00)00034-3 -
Neuroscience Jan 2017The M-current (I) is a voltage-dependent, persistent K current so termed because it is strongly inhibited by the cholinergic agonist muscarine. The I main function is to...
The M-current (I) is a voltage-dependent, persistent K current so termed because it is strongly inhibited by the cholinergic agonist muscarine. The I main function is to limit neuronal excitability by contrasting action potential firing. Although motoneurons are sensitive to acetylcholine, the role of I in modulating their excitability is still controversial. The aim of the present report was to examine the presence of I in hypoglossal motoneurons (HMs) and its role in the modulation of firing properties using an in vitro model of rat brainstem slice. For this purpose, we employed the whole-cell patch-clamp technique to record HM responses upon stimulation with either a standard I deactivation voltage protocol or depolarizing current steps. Voltage commands from depolarized potential induced inward relaxations with the common characteristics of I, comprising inhibition by either muscarine (10μM) or the selective I inhibitor linopirdine (30μM). I was pharmacologically distinguished from the hyperpolarization-activated inward-rectifying current and, within the -20 to -50mV range, deactivated with >100-ms time constant. Current-clamp experiments demonstrated that I strongly regulated HM action potential firing, since both muscarine and linopirdine increased spike frequency whereas the M-channel opener retigabine (20μM) reduced it. Conversely, I seemed uninvolved in the generation of the medium afterhyperpolarizing potential. Our results suggest that HMs possess I, whose pharmacological modulation is an important tool to up- or down-regulate excitability, to be explored in experimental models of neurodegeneration.
Topics: Animals; Hypoglossal Nerve; Indoles; Membrane Potentials; Motor Neurons; Muscarine; Neurotransmitter Agents; Patch-Clamp Techniques; Potassium Channels; Pyridines; Rats, Wistar; Tissue Culture Techniques
PubMed: 27984184
DOI: 10.1016/j.neuroscience.2016.10.048 -
Receptors & Channels 1995Putative M-type K(+)-channels ('M-channels') were recorded in differentiated NG108-15 neuroblastoma x glioma hybrid cells transformed to express m1 muscarinic...
Putative M-type K(+)-channels ('M-channels') were recorded in differentiated NG108-15 neuroblastoma x glioma hybrid cells transformed to express m1 muscarinic acetylcholine receptors using cell-attached patch-electrodes. Channels showed multiple conductances, with peaks at 6-9 and 12-15 pS. Averaged currents showed time-dependent activation during 1 s depolarization steps to around -30 mV. Steady-state Po increased in a voltage-dependent manner when the membrane was depolarized between 10 and 60 mV, with a limiting slope of 5.5 mV/e-fold change in Po. Steady-state kinetics were fit by two open and three shut times: depolarization shortened shut times and lengthened open times. Application of muscarine (10 microM) or bradykinin (10 microM) to the membrane outside the patch reversibly reduced steady-state in-patch channel activity to 38.4 +/- 11.7 and 28.8 +/- 6.1% of control values, respectively. Inhibition was accompanied by a lengthening of channel shut times without significant change in open times or distribution of conductance levels. No effect of muscarine or bradykinin on whole-cell or membrane patch delayed rectifier currents was detected. It is concluded that M-channels in NG108-15 cells are qualitatively similar to, but sparser than, those previously reported in rat sympathetic neurones. Their inhibition by extra-patch acetylcholine and bradykinin suggests that a mobile messenger is involved in the transduction process leading from receptor activation to channel closure.
Topics: Animals; Bradykinin; Cell Line, Transformed; Glioma; Hybrid Cells; Ion Channel Gating; Kinetics; Membrane Potentials; Mice; Muscarine; Muscarinic Agonists; Neuroblastoma; Potassium Channel Blockers; Potassium Channels; RNA, Messenger; Rats; Swine
PubMed: 8581401
DOI: No ID Found