scholarly journals Acetylcholine Signaling Genes are Required for Cocaine-Stimulated Egg Laying in Caenorhabditis elegans

2021 ◽  
Author(s):  
Soren Emerson ◽  
Megan Hay ◽  
Mark Smith ◽  
Ricky Granger ◽  
David Blauch ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Nicotinic Acetylcholine Receptors ◽  
Intracellular Signaling ◽  
Acetylcholine Receptors ◽  
Egg Laying ◽  
Signaling Cascades ◽  
Synthetic Enzymes ◽  
Degradative Enzymes ◽  
Cholinergic Effects

Abstract The toxicity and addictive liability associated with cocaine abuse are well known. However, its mode of action is not completely understood, and effective pharmacotherapeutic interventions remain elusive. The cholinergic effects of cocaine on acetylcholine receptors, synthetic enzymes, and degradative enzymes have been the focus of relatively little empirical investigation. Due to its genetic tractability and anatomical simplicity, the egg laying circuit of the hermaphroditic nematode, Caenorhabditis elegans, is a powerful model system to precisely examine the genetic and molecular targets of cocaine in vivo. Here, we report a novel cocaine-induced behavioral phenotype in Caenorhabditis elegans, cocaine-stimulated egg laying. In addition, we present the results of an in vivo candidate suppression screen of synthetic enzymes, receptors, degradative enzymes, and downstream components of the intracellular signaling cascades of the main neurotransmitter systems that control Caenorhabditis elegans egg laying. Our results show that cocaine-stimulated egg laying is dependent on acetylcholine synthesis and synaptic release, functional nicotinic acetylcholine receptors, and the Caenorhabditis elegans acetylcholinesterases.

scholarly journals Acetylcholine Signaling Genes are Required for Cocaine-Stimulated Egg Laying in Caenorhabditis elegans

2020 ◽  
Author(s):  
Soren Emerson ◽  
Megan Hay ◽  
Mark Smith ◽  
David Blauch ◽  
Nicole Snyder ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Nicotinic Acetylcholine Receptors ◽  
Intracellular Signaling ◽  
Acetylcholine Receptors ◽  
Egg Laying ◽  
Synthetic Enzymes ◽  
C Elegans ◽  
Degradative Enzymes ◽  
Serotonin Reuptake Transporter

Despite the toxicity and addictive liability associated with cocaine abuse, its mode of action is not completely understood, and effective pharmacotherapeutic interventions remain elusive. The cholinergic effects of cocaine on acetylcholine receptors, synthetic enzymes, and degradative enzymes have been the focus of relatively little empirical investigation. Due to its genetic tractability and anatomical simplicity, the egg laying circuit of the hermaphroditic nematode, Caenorhabditis elegans, is a powerful model system to precisely examine the genetic and molecular targets of cocaine in vivo. Here, we report a novel cocaine-induced phenotype in Caenorhabditis elegans, cocaine-stimulated egg laying. In addition, we present the results of an in vivo candidate screen of synthetic enzymes, receptors, degradative enzymes, and downstream components of the intracellular signaling cascades of the main neurotransmitter systems that control Caenorhabditis elegans egg laying. Our results show that cocaine-stimulated egg laying is dependent on acetylcholine synthesis and synaptic release, functional nicotinic acetylcholine receptors, and the Caenorhabditis elegans acetylcholinesterases. Further, we show that cocaine-stimulated egg laying is not dependent on other neurotransmitters besides acetylcholine, including serotonin, dopamine, octopamine, and tyramine. Finally, our data show that cocaine-stimulated egg laying is increased in mutants for the C. elegans serotonin reuptake transporter as well as mutants for a 5-HT-gated chloride channel likely expressed in the locomotion circuit. Together, these results highlight serotonergic inhibition of egg laying behavior, functional connectivity between the egg laying and locomotion circuits in Caenorhabditis elegans, and possible discrete cholinergic and serotonergic effects of cocaine in the egg laying and locomotion circuits, respectively.

scholarly journals Genes Affecting the Activity of Nicotinic Receptors Involved in Caenorhabditis elegans Egg-Laying Behavior

Genetics ◽  
2001 ◽  
Vol 157 (4) ◽  
pp. 1599-1610
Author(s):  
Jinah Kim ◽  
Daniel S Poole ◽  
Laura E Waggoner ◽  
Anthony Kempf ◽  
David S Ramirez ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Nicotinic Acetylcholine Receptors ◽  
Nicotinic Receptor ◽  
Molecular Basis ◽  
Acetylcholine Receptors ◽  
Nicotinic Receptors ◽  
Receptor Gene ◽  
Egg Laying ◽  
Cholinergic Neurotransmission ◽  
Stimulation Of

Abstract Egg-laying behavior in Caenorhabditis elegans is regulated by multiple neurotransmitters, including acetylcholine and serotonin. Agonists of nicotinic acetylcholine receptors such as nicotine and levamisole stimulate egg laying; however, the genetic and molecular basis for cholinergic neurotransmission in the egg-laying circuitry is not well understood. Here we describe the egg-laying phenotypes of eight levamisole resistance genes, which affect the activity of levamisole-sensitive nicotinic receptors in nematodes. Seven of these genes, including the nicotinic receptor subunit genes unc-29, unc-38, and lev-1, were essential for the stimulation of egg laying by levamisole, though they had only subtle effects on egg-laying behavior in the absence of drug. Thus, these genes appear to encode components of a nicotinic receptor that can promote egg laying but is not necessary for egg-laying muscle contraction. Since the levamisole-receptor mutants responded to other cholinergic drugs, other acetylcholine receptors are likely to function in parallel with the levamisole-sensitive receptors to mediate cholinergic neurotransmission in the egg-laying circuitry. In addition, since expression of functional unc-29 in muscle cells restored levamisole sensitivity under some but not all conditions, both neuronal and muscle cell UNC-29 receptors are likely to contribute to the regulation of egg-laying behavior. Mutations in one levamisole receptor gene, unc-38, also conferred both hypersensitivity and reduced peak response to serotonin; thus nicotinic receptors may play a role in regulating serotonin response pathways in the egg-laying neuromusculature.

N-cholinergic facilitation of glutamate release from an individual retinotectal fiber in frog

2001 ◽  
Vol 18 (4) ◽  
pp. 549-558 ◽  
Author(s):  
A. KURAS ◽  
N. GUTMANIENĖ
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Action Potentials ◽  
Acetylcholine Receptors ◽  
Kynurenic Acid ◽  
Glutamate Release ◽  
Synaptic Potentials ◽  
Lower Vertebrates ◽  
Optic Fibers ◽  
Retinotectal Transmission

Nicotinic acetylcholine receptors are localized on retinotectal axons' terminals in lower vertebrates. The effects of activation of these receptors by endogenous acetylcholine were observed under stimulation of mass optic fibers. This study was designed to determine whether endogenous acetylcholine facilitates frog retinotectal transmission, provided only the synapses of an individual optic axon are activated, and to evaluate the feasible extent of nicotinic facilitation in these synapses by applied agonist. To this end, the effects of cholinergic drugs on the extracellular action and synaptic potentials recorded from the terminal arborization of a separate retinotectal fiber (in layer F of the tectum) were investigated in vivo. Glutamatergic nature of retinotectal synapses was reexamined by treatment with kynurenic acid. Both kynurenic acid (0.25–1 mM) and d-tubocurarine chloride (10–15 μM) significantly depressed the synaptic potentials. Carbamylcholine chloride (50–150 μM) evoked a large augmentation of the synaptic potentials and a slight but statistically significant decrease of the action potentials. D-tubocurarine reduced the effect of carbamylcholine. Pilocarpine hydrochloride (50 μM) had only a weak effect. The paired-pulse facilitation of the synaptic potentials changed significantly under the action of carbamylcholine and d-tubocurarine. The obtained results suggest that the glutamate release from activated synapses of individual retinotectal axons is facilitated by endogenous acetylcholine via presynaptic nicotinic receptors. Under used stimulation conditions, this modulation mechanism was employed only partially since its activation by applied carbamylcholine could enhance synaptic transmission up to 2.8 times.

scholarly journals The Prototoxin lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival In Vivo

Neuron ◽  
2006 ◽  
Vol 51 (5) ◽  
pp. 587-600 ◽  
Author(s):  
Julie M. Miwa ◽  
Tanya R. Stevens ◽  
Sarah L. King ◽  
Barbara J. Caldarone ◽  
Ines Ibanez-Tallon ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine

scholarly journals The Caenorhabditis elegans DEG-3/DES-2 Channel Is a Betaine-Gated Receptor Insensitive to Monepantel

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 312
Author(s):  
Tina V. A. Hansen ◽  
Heinz Sager ◽  
Céline E. Toutain ◽  
Elise Courtot ◽  
Cédric Neveu ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Parasitic Nematode ◽  
Nematode Species ◽  
Xenopus Laevis Oocytes ◽  
Allosteric Modulators ◽  
C Elegans ◽  
Electrode Voltage ◽  
Insight Into

Natural plant compounds, such as betaine, are described to have nematocidal properties. Betaine also acts as a neurotransmitter in the free-living model nematode Caenorhabditis elegans, where it is required for normal motility. Worm motility is mediated by nicotinic acetylcholine receptors (nAChRs), including subunits from the nematode-specific DEG-3 group. Not all types of nAChRs in this group are associated with motility, and one of these is the DEG-3/DES-2 channel from C. elegans, which is involved in nociception and possibly chemotaxis. Interestingly, the activity of DEG-3/DES-2 channel from the parasitic nematode of ruminants, Haemonchus contortus, is modulated by monepantel and its sulfone metabolite, which belong to the amino-acetonitrile derivative anthelmintic drug class. Here, our aim was to advance the pharmacological knowledge of the DEG-3/DES-2 channel from C. elegans by functionally expressing the DEG-3/DES-2 channel in Xenopus laevis oocytes and using two-electrode voltage-clamp electrophysiology. We found that the DEG-3/DES-2 channel was more sensitive to betaine than ACh and choline, but insensitive to monepantel and monepantel sulfone when used as direct agonists and as allosteric modulators in co-application with betaine. These findings provide important insight into the pharmacology of DEG-3/DES-2 from C. elegans and highlight the pharmacological differences between non-parasitic and parasitic nematode species.

scholarly journals Prospects for use of peptides and their derivatives, structurally corresponding to the G protein-coupled receptors, in medicine

2015 ◽  
Vol 61 (1) ◽  
pp. 19-29 ◽  
Author(s):  
A.O. Shpakov ◽  
E.A. Shpakova
Keyword(s):  
G Protein ◽  
Intracellular Signaling ◽  
High Efficiency ◽  
Clinical Medicine ◽  
Inflammatory Diseases ◽  
G Protein Coupled Receptors ◽  
Signaling Cascades ◽  
G Protein Coupled

The regulation of signaling pathways involved in the control of many physiological functions is carried out via the heterotrimeric G protein-coupled receptors (GPCR). The search of effective and selective regulators of GPCR and intracellular signaling cascades coupled with them is one of the important problems of modern fundamental and clinical medicine. Recently data suggest that synthetic peptides and their derivatives, structurally corresponding to the intracellular and transmembrane regions of GPCR, can interact with high efficiency and selectivity with homologous receptors and influence, thus, the functional activity of intracellular signaling cascades and fundamental cellular processes controlled by them. GPCR-peptides are active in both in vitro and in vivo. They regulate hematopoiesis, angiogenesis and cell proliferation, inhibit tumor growth and metastasis, and prevent the inflammatory diseases and septic shock. These data show greatest prospects in the development of the new generations of drugs based on GPCR-derived peptides, capable of regulating the important functions of the organism.

scholarly journals Effects of preganglionic denervation and postganglionic axotomy on acetylcholine receptors in the chick ciliary ganglion.

1987 ◽  
Vol 105 (4) ◽  
pp. 1847-1854 ◽  
Author(s):  
M H Jacob ◽  
D K Berg
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Time Course ◽  
Ciliary Ganglion ◽  
Ciliary Ganglion Neurons ◽  
Membrane Components ◽  
Ganglion Neurons ◽  
Alpha Bungarotoxin ◽  
Binding Component

The regulation of nicotinic acetylcholine receptors (AChRs) in chick ciliary ganglia was examined by using a radiolabeled anti-AChR mAb to quantitate the amount of receptor in ganglion detergent extracts after preganglionic denervation or postganglionic axotomy. Surgical transection of the preganglionic input to the ciliary ganglion in newly hatched chicks caused a threefold reduction in the total number of AChRs within 10 d compared with that present in unoperated contralateral control ganglia. Surgical transection of both the choroid and ciliary nerves emerging from the ciliary ganglion in newly hatched chicks to establish postganglionic axotomy led to a nearly 10-fold reduction in AChRs within 5 d compared with unoperated contralateral ganglia. The declines were specific since they could not be accounted for by changes in ganglionic protein or by decreases in neuronal survival or size. Light microscopy revealed no gross morphological differences between neurons in operated and control ganglia. A second membrane component of cholinergic relevance on chick ciliary ganglion neurons is the alpha-bungarotoxin (alpha-Bgt)-binding component. The alpha-Bgt-binding component also declined in number after either postganglionic axotomy or preganglionic denervation, but appeared to do so with a more rapid time course than did ganglionic AChRs. The results imply that cell-cell interactions in vivo specifically regulate both the number of AChRs and the number of alpha-Bgt-binding components in the ganglion. Regulation of these neuronal cholinergic membrane components clearly differs from that previously described for muscle AChRs.

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