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Among the plants that exhibit significant or established pharmacological activity, the genus Artemisia L. deserves special attention. This genus comprises over 500 species belonging to the largest Asteraceae family. Our study aimed at providing a comprehensive evaluation of the phytochemical composition of the ethanol extracts of five different Artemisia L. species (collected from the southwest of the Russian Federation) and their antimicrobial and nematocide activity as follows: A. annua cv. Novichok., A. dracunculus cv. Smaragd, A. santonica cv. Citral, A. abrotanum cv. Euxin, and A. scoparia cv. Tavrida. The study of the ethanol extracts of the five different Artemisia L. species using the methods of gas chromatography–mass spectrometry (GC–MS) and high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (HPLC–MS/MS) allowed establishing their phytochemical profile. The obtained data on the of five different Artemisia L. species ethanol extracts' phytochemical composition were used to predict the antibacterial and antifungal activity against phytopathogenic microorganisms and nematocidal activity against the free-living soil nematode Caenorhabditis elegans. The major compounds found in the composition of the Artemisia L. ethanol extracts were monoterpenes, sesquiterpenes, flavonoids, flavonoid glycosides, coumarins, and phenolic acids. The antibacterial and antifungal activity of the extracts began to manifest at a concentration of 150 µg/mL. The A. dracunculus cv. Smaragd extract had a selective effect against Gram-positive R. iranicus and B. subtilis bacteria, whereas the A. scoparia cv. Tavrida extract had a selective effect against Gram-negative A. tumefaciens and X. arboricola bacteria and A. solani, R. solani and F. graminearum fungi. The A. annua cv. Novichok, A. dracunculus cv. Smaragd, and A. santonica cv. Citral extracts in the concentration range of 31.3–1000 µg/mL caused the death of nematodes. It was established that A. annua cv. Novichok affects the UNC-63 protein, the molecular target of which is the nicotine receptor of the N-subtype. [ABSTRACT FROM AUTHOR]

In several central nervous system diseases, it has been reported that inflammation may be related to the etiologic process, therefore, therapeutic strategies are being implemented to control inflammation. As the nervous system and the immune system maintain close bidirectional communication in physiological and pathological conditions, the modulation of inflammation through the cholinergic anti-inflammatory reflex has been proposed. In this review, we summarized the evidence supporting chemical stimulation with cholinergic agonists and vagus nerve stimulation as therapeutic strategies in the treatment of various central nervous system pathologies, and their effect on inflammation.

Nicotinic α‐7 acetylcholine receptor (nAChRα7) is a critical regulator of cholinergic anti‐inflammatory actions in several diseases, including acute respiratory distress syndrome(ARDS). Given the potential importance of α7nAChR as a therapeutic target, we evaluated whether PNU‐282987, an α7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6 mice. PNU‐282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL‐ 1β, TNF‐α, IL‐6, keratinocyte chemoattractant (KC), and IL‐10 cytokine levels in the bronchoalveolar lavage fluid (P> 0.05). In addition, lung NF‐κB phosphorylation decreased, along with collagen fiber deposition and the number of matrix metalloproteinase‐9+ and −2+ cells, whereas the number of tissue inhibitor of metalloproteinase‐1+ cells increased (P < 0.05). PNU‐282987 treatment also reduced lung mRNA levels and the frequency of M1 macrophages, whereas cells expressing the M2‐related markers CD206 and IL‐10 increased, suggesting changes in the macrophage profile. Finally, PNU‐282987 improved lung function in LPS‐treated animals. The collective results suggest that PNU‐282987, anagonist of α7nAChR, reducesLPS‐induced experimental ALI, thus supporting the notion that drugs that act on α7nAChRs should be explored for ARDS treatment in humans.—Pinheiro, N. M., Santana, F. P. R., Almeida, R. R., Guerreiro, M., Martins, M.A., Caperuto, L.C., Câmara, N.O.S., Wensing, L.A., Prado, V. F., Tibério, I. F. L. C., Prado, M.A.M., Prado, C. M. Acute lung injury is reduced by the α7nAChR agonist PNU‐282987 through changes in the macrophage profile. FASEB J. 31, 320–332 (2017) www.fasebj.org [ABSTRACT FROM AUTHOR]

Schizophrenia is a severe psychiatric disorder with a core component of impaired cognitive function still remaining as one of the greatest challenges in the pharmacological treatment of the disorder. The CHRNA7 gene, encoding the subunit of the human α7 nicotinic acetylcholine receptor (αnAChR), is suggested as a susceptibility factor for schizophrenia. CHRNA7 has also been genetically linked to the P50 auditory evoked potential deficit, a candidate endophenotype of schizophrenia, but not to prepulse inhibition of the startle reflex (PPI). In this study, 95 antipsychotic-naïve schizophrenic patients and 450 unaffected controls were screened for CHRNA7 promoter variants to investigate the association with schizophrenia, P50 suppression and PPI. We found that the promoter variant -194C (rs28531779) was significantly associated with schizophrenia, but did not find any association of this variant with P50 suppression or PPI. In addition, individuals with CHRNA7 promoter variants had elevated startle magnitude in pulse-alone trials compared to individuals without a variant. The present findings provide further support for a role of the αnAChR in schizophrenia and show a genetic link between CHRNA7 and startle magnitude, indicating that cholinergic neurotransmission involving the αnAChR could be involved in sensory registration processes. [ABSTRACT FROM AUTHOR]

Over the last several years we have synthesized and studied the in vitro and in vivo nAChR pharmacological properties of epibatidine ( 4 ) analogs. In this study we report the synthesis, nAChR in vitro and in vivo pharmacological properties of 3′-(substituted pyridinyl)-deschloroepibatidine analogs ( 5a – e and 6a – e ). All of the analogs had high binding affinity for α4β2 ∗ -nAChRs. Several of the analogs were potent antagonists of α4β2-nAChRs in in vitro efficacy tests and were potent antagonists of nicotine-induced antinociception in the mouse tail-flick test. Compound 6b had a K i = 0.13 nM in the binding assay, 25- and 46-fold selectivity for the α4β2 ∗ -nAChR relative to the α3β4- and α7-nAChR, respectively, in the in vitro efficacy test and an AD 50 = 0.13 μg/kg in the tail-flick test. Combined with favorable calculated physiochemical properties compared to varenicline, our findings suggest that 6b should be considered for development as a potential pharmacotherapy for treating nicotine addiction and other CNS disorders. [ABSTRACT FROM AUTHOR]

The caudal nucleus of the solitary tract (NTS) serves as the site of the first synapse for visceral sensory inputs to the central nervous system. The NTS sends functional projections to multiple brain nuclei, with gastric-related projections primarily targeting the dorsal motor nucleus of the vagus (DMV). Previous studies have demonstrated that the majority of caudal NTS neurons that project to the DMV respond robustly to nicotine and express nicotinic acetylcholine receptors (nAChRs). However, the cytochemical identity and relationship with specific viscera of DMV-projecting, nicotine-responsive caudal NTS neurons have not been determined. The present study used transgenic mice that express enhanced green fluorescent protein (EGFP) under a GAD67 promoter in a subset of GABAergic neurons, in vivo retrograde pseudorabies viral labeling to identify gastric-related vagal complex neurons, and patch-clamp electrophysiology in acute brain stem slices to test the hypothesis that gastric-related and GABAergic inhibitory synaptic input to the DMV from the caudal NTS is under a robust modulatory control by nAChRs. Our results suggest that activation of nAChRs in the caudal NTS, but not DMV, potentiates GABAergic, but not glutamatergic, input to the DMV. Gastric-related caudal NTS and DMV neurons are directly involved in this nicotine-sensitive circuitry. Understanding the central patterns of nicotinic modulation of visceral sensory-motor circuitry may help develop therapeutic interventions to restore autonomic homeostasis in patients with autonomic impairments. [ABSTRACT FROM AUTHOR]

Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10-1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical studies have demonstrated that both PPI and cognitive function can be enhanced by nicotine. PPI has been shown to be mediated, at least in part, by mesopontine cholinergic neurons that project to pontine startle neurons and activate muscarinic and potentially nicotine receptors (nAChRs). The subtypes and anatomical location of nAChRs involved in mediating and modulating PPI remain unresolved. We tested the hypothesis that nAChRs that are expressed by pontine startle neurons contribute to PPI. We also explored whether or not these pontine receptors are responsible for the nicotine enhancement of PPI. While systemic administration of nAChR antagonists had limited effects on PPI, PnC microinfusions of the non-α7nAChR preferring antagonist TMPH, but not of the α7nAChR antagonist MLA, into the PnC significantly reduced PPI. Electrophysiological recordings from startle-mediating PnC neurons confirmed that nicotine affects excitability of PnC neurons, which could be antagonized by TMPH, but not by MLA, indicating the expression of non-α7nAChR. In contrast, systemic nicotine enhancement of PPI was only reversed by systemic MLA and not by TMPH or local microinfusions of MLA into the PnC. In summary, our data indicate that non-α7nAChRs in the PnC contribute to PPI at stimulus intervals of 100ms or less, whereas activation of α7nAChRs in other brain areas is responsible for the systemic nicotine enhancement of PPI. This is important knowledge for the correct interpretation of behavioral, preclinical, and clinical data as well as for developing drugs for the amelioration of PPI deficits and the enhancement of cognitive function. [ABSTRACT FROM AUTHOR]

The role of acetylcholine and specific nicotinic receptors in sensorimotor gating and higher cognitive function has been controversial. Here, we used a commercially available mouse with a null mutation in the Chrna7tm1Bay gene [α7-nicotinic acetylcholine receptor ( nAChR) knockout ( KO) mouse] in order to assess the role of the α7- nAChR in sensorimotor gating and spatial learning. We examined prepulse inhibition ( PPI) of startle and nicotine-induced enhancement of PPI. We also tested short- and long-term habituation of the startle response as well as of locomotor behaviour in order to differentiate the role of this receptor in the habituation of evoked behaviour (startle) vs. motivated behaviour (locomotion). To address higher cognition, mice were also tested in a spatial learning task. Our results showed a mild but consistent PPI deficit in α7- nAChR KO mice. Furthermore, they did not show nicotine-induced enhancement of startle or PPI. Short- and long-term habituation was normal in KO mice for both types of behaviours, evoked or motivated, and they also showed normal learning and memory in the Barnes maze. Thorough analysis of the behavioural data indicated a slightly higher degree of anxiety in α7- nAChR KO mice; however, this could only be partially confirmed in an elevated plus maze test. In summary, our data suggest that α7- nAChRs play a minor role in PPI, but seem to mediate nicotine-induced PPI enhancement. We found no evidence to suggest that they are important for habituation or spatial learning. [ABSTRACT FROM AUTHOR]

Abstract: The beneficial effect of nicotine has been reported in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) patients, but not tested in sporadic cases. Recently, a nicotine defect in the arousal pathway has been hypothesized even in sporadic NFLE patients and their relatives. This case–control family study was designed to test whether NFLE subjects were more likely to use tobacco than controls, as an indirect marker of cholinergic arousal system dysregulation. At least four relatives were included for each NFLE proband and control. Each subject was questioned about tobacco habits; 434 individuals were recruited. Moreover, we compared NFLE patients with age- and sex-matched controls to determine whether they are more likely to use tobacco. We found a slightly higher trend of tobacco use in NFLE probands compared to that in control subjects; we did not find any significant difference in the distribution of tobacco use among NFLE group compared to that in the control group. [Copyright &y& Elsevier]

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In several central nervous system diseases, it has been reported that inflammation may be related to the etiologic process, therefore, therapeutic strategies are being implemented to control inflammation. As the nervous system and the immune system maintain close bidirectional communication in physiological and pathological conditions, the modulation of inflammation through the cholinergic anti-inflammatory reflex has been proposed. In this review, we summarized the evidence supporting chemical stimulation with cholinergic agonists and vagus nerve stimulation as therapeutic strategies in the treatment of various central nervous system pathologies, and their effect on inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Startle responses are attenuated by prepulse inhibition (PPI), which is considered to reflect a sensorimotor gating mechanism and is impaired in patients suffering from schizophrenia. A midbrain circuit that mediates PPI in rats has been proposed and behavioral experiments have indicated an important role of acetylcholine and GABA in inhibiting startle. We here test the hypothesis that activation of the midbrain neurons can inhibit startle signaling through a cholinergic mechanism. We have developed a brain slice that comprises startle mediating giant pontine neurons as well as midbrain mesopontine neurons required for PPI. Patch clamp recordings of startle mediating brainstem neurons combined with stimulation of sensory afferents within the startle pathway and activation of mesopontine neurons revealed a delayed inhibition of synaptic transmission 300 ms and 1 s after midbrain activation. The latter was reversed by the muscarinic antagonist scopolamine. Further, there was a shift in the paired pulse ratio 1 s but not 300 ms after midbrain stimulation. Our results show that there is a direct cholinergic projection from the proposed PPI midbrain circuit to startle mediating neurons in the brainstem and that this projection inhibits synaptic transmission in the startle pathway in a distinct time window through the activation of presynaptic muscarinic receptors. Moreover, there is indication for a different receptor that mediates inhibition through this projection in a shorter time window and is located postsynaptically. Our results contribute to the understanding of mechanisms underlying PPI, which is important for developing new targets in the treatment of disorders accompanied with pre-attentive cognitive deficits. [Copyright &y& Elsevier]

The article focuses on a study which examined the efficacy of varenicline, an alpha4beta2 nicotinic receptor partial agonist, in relieving nicotine craving and withdrawal symptoms while reducing the reinforcing effects of nicotine. The physiological effects of the drug on inducing smoking cessation and maintaining smoking abstinence are evaluated. The methodology and results of the study are presented.

18-Methoxycoronaridine, a novel iboga alkaloid congener that decreases drug self-administration in several animal models, may be a potential treatment for multiple forms of drug abuse. In previous work, 18-methoxycoronaridine was found to be a somewhat selective antagonist at α3β4 nicotinic receptors; and low dose combinations of 18-methoxycoronaridine with other drugs known to have the same action (e.g., mecamylamine, dextromethorphan) decreased both morphine and methamphetamine self-administration in rats at doses that were ineffective if administered alone. In the present study, similar drug combinations (but including bupropion as well) were found to decrease nicotine self-administration in rats. The data further support the hypothesis that diencephalic pathways having high densities of α3β4 nicotinic receptors modulate mesocorticolimbic pathways more directly involved in drug reinforcement. Antagonists of α3β4 nicotinic receptors may represent a totally novel approach to treating polydrug abuse. [Copyright &y& Elsevier]

Nicotine is one of the most representative components in cigarette smoke leading to gastric ulceration. Both ornithine decarboxylase and potassium ion (K+) channels are essential for cell growth and wound repair. The aim of the present study is to elucidate the causative relationship of these two factors during wound healing and the influence of nicotine on this healing process in rat gastric mucosal epithelial cells (RGM-1). Nicotine markedly inhibited cell migration and proliferation in RGM-1 cells. The latter effect was significantly antagonized by a nicotinic receptor blocker, mecamylamine. Nicotine also suppressed ornithine decarboxylase activity significantly. Our data showed that inhibition of cell proliferation and ornithine decarboxylase activity by nicotine was accompanied with a reduction in K+ channel protein expression, all of which were significantly alleviated by spermidine pretreatment. These results suggested that there was a cause/effect link between ornithine decarboxylase and K+ channel on wound repair. Nicotine in cigarette smoke inhibited this healing process and delayed wound repair in gastric epithelial cells. [Copyright &y& Elsevier]

The iboga alkaloid ibogaine and the novel iboga alkaloid congener 18-methoxycoronaridine are putative anti-addictive agents. Using patch–clamp methodology, the actions of ibogaine and 18-methoxycoronaridine at various neurotransmitter receptor ion-channel subtypes were determined. Both ibogaine and 18-methoxycoronaridine were antagonists at α3β4 nicotinic receptors and both agents were more potent at this site than at α4β2 nicotinic receptors or at NMDA or 5-HT3 receptors; 18-methoxycoronaridine was more selective in this regard than ibogaine. In studies of morphine and methamphetamine self-administration, the effects of low dose combinations of 18-methoxycoronaridine with mecamylamine or dextromethorphan and of mecamylamine with dextromethorphan were assessed. Mecamylamine and dextromethorphan have also been shown to be antagonists at α3β4 nicotinic receptors. All three drug combinations decreased both morphine and methamphetamine self-administration at doses that were ineffective if administered alone. The data are consistent with the hypothesis that antagonism at α3β4 receptors is a potential mechanism to modulate drug seeking behavior. 18-Methoxycoronaridine apparently has greater selectivity for this site than other agents and may be the first of a new class of synthetic agents acting via this novel mechanism to produce a broad spectrum of anti-addictive activity. [Copyright &y& Elsevier]

This review addresses the synthesis and characterization of two different types of receptor-based liquid chromatographic supports, one based upon a trans-membrane ligand gated ion channel receptor (the nicotinic acetylcholine receptor) and the other a soluble nuclear receptor (the estrogen receptor). In addition, studies with the P-glycoprotein transporter are also reported. The nicotinic receptor was immobilized via hydrophobic insertion into the interstitial spaces of an immobilized artificial membrane (IAM) stationary phase, the estrogen receptor was tethered to a hydrophilic stationary phase and the membranes containing the Pgp transporter were coated on the surface of the IAM stationary phase. The stationary phases were characterized using known ligands and substrates for the respective non-immobilized proteins. The results from zonal and frontal chromatographic experiments demonstrated that the stationary phases could be used to determine binding affinities (expressed as dissociation constants, Kd’s) and to resolve mixtures of ligands according to their relative affinities. In addition, competitive ligand binding studies on the P-glycoprotein-based stationary phase have established that this phase can be used to identify and characterize competitive displacement and allosteric interactions. These studies demonstrate that immobilized-receptor phases can be used for on-line pharmacological studies and as rapid screens for the isolation and identification of lead drug candidates from complex biological or chemical mixtures. [Copyright &y& Elsevier]

Several alkaloids are toxic to insects and vertebrates and, in addition, can inhibit the growth of bacteria and plant seedlings. In vitro assays were established to elucidate their modes of action and to understand their allelochemical properties. Basic molecular targets studied, present in all cells, included DNA intercalation, protein biosynthesis, and membrane stability. The degree of DNA intercalation was positively correlated with inhibition of DNA polymerase I, reverse transcriptase, and translation at the molecular level and with toxicity against insects and vertebrates at an organismic level. Inhibition of protein biosynthesis was positively correlated with animal toxicity. Molecular targets studied, present only in animals, included neuroreceptors (alpha1, alpha2, serotonin, muscarinic, and nicotinic acetylcholine receptors) and enzymes related to acetylcholine (acetylcholine esterase and choline acetyltransferase). The degree of binding of alkaloids to adrenergic, serotonin, and muscarinic acetylcholine receptors was positively correlated in G-protein-coupled receptors. Receptor binding and toxicity was correlated in insects. The biochemical properties of alkaloids are discussed. It is postulated that their structures were shaped in a process termed “evolutionary molecular modeling” to interact with a single and, more often, with several molecular targets at the same time. Many alkaloids are compounds with a broad activity spectrum that apparently have evolved as “multipurpose” defense compounds. The evolution of allelochemicals affecting more than one target could be a strategy to counteract adaptations by specialists and to help fight off different groups of enemies. [ABSTRACT FROM AUTHOR]

Isolated segements of the guinea pig ileum were vascularly perfused and the release of 5-HT and its metabolite 5-HIAA into the portal venous effluent determined by HPLC with electrochemical detection. Test substances were applied via the arterial perfusion medium. Oxotremorine inhibited concentration-dependently the release of 5-HT and 5-HIAA (by 47% at 1 μmol/l). Scopolamine (0.1 μmol/1) did not affect the release of 5-HT and 5-HIAA, but antagonized the effect of oxotremorine. In the presence of TTX (1 μmol/1) oxotremorine (1 pmol/1) increased the release of 5-HT by 150% and that of 5-HIAA by 220%. This increase was completely blocked by scopolamine. Hexamethonium (100 pmol/1) and TTX (1 pmol/1) reduced the release of 5-HT by 32 and 40%, respectively. DMPP (10 pmol/1) increased the release of 5-HT by 57%, and this effect was prevented by hexamethonium. Neither DMPP nor hexamethonium significantly affected the release of 5-HIAA. The enhancing effect of DMPP on 5-HT release was increased and prolonged in the presence of TTX or scopolamine. Nicotine (1, 10 or 30 μmol/l) alone did not cause a consistent increase in the release of 5-HT. However, in the presence of scopolamine nicotine increased the release of 5-HT by 57%. In conclusion, the release of intestinal 5-HT is facilitated via muscarine and nicotine receptors located on the enterochromaffin cells. Indirect evidence suggests that the release of 5-HT is additionally modulated by an as yet unknown inhibitory neurotransmitter released by muscarine receptor activation. [ABSTRACT FROM AUTHOR]

El tabaquismo debe ser considerado como una drogodependencia. La nicotina es su principal ingrediente psicoactivo y debe sus propiedades adictivas al aumento de la liberación de dopamina en los circuitos de recompensa, por su acción agonista sobre receptores colinérgicos nicotínicos . La estimulación indirecta sobre otros sistemas de neurotransmisión, como el noradrenérgico y el cannabinoide, ha sido implicada en sus propiedades reforzadoras. Exponer este enfoque molecular del tabaquismo, el cual descubre los blancos susceptibles a ser modificados por intervenciones farmacológicas, es el objetivo de este trabajo. Las estrategias actuales incluyen la terapia sustitutiva con nicotina, el uso de fármacos antidepresivos y el desarrollo de vacunas. El tratamiento del tabaquismo implica además la consideración de medidas impositivas, legislativas y laborales y, sobre todo, un cambio de conducta, lo que sumado al apoyo farmacológico constituye un modo eficaz de reducir la morbimortalidad derivada del tabaco a corto y largo plazos.Smoking must be considered as a drug dependence.Nicotine is its main psicoactive ingredient and it ows its addictive propieties to the increase of dopamine liberation in the reward circuits, due to its agonist action on the nicotinic cholinergic receptors. Non direct stimulation over other neurotransmission systems, such as the noradrenergic and cannabinoid, has been involved in its reinforcing propieties. The main of this paper is to express the molecular approach of smoking , which uncovers the susceptible targets to be modified by pharmacological interventions. The current strategies include the substitutive therapy with nicotine, the use of antidepressants and the development of vaccines. The treatment of the smoking habit involves a series of regulations and legislations ; must of all, it involves a change of behavior, which in conjunction with the pharmacological support, it is an efficacious way of reducing the morbidity and mortality derived from tobacco at a short and a long term.

Background/aim: The purpose of our study was to test whether EBV infection affects the response of human breast cancer cells to nicotine. In addition, the underlying signaling mechanisms were evaluated., Materials and Methods: EBV-infected MDA-MB-231 and LMP1-transfected MDA-MB-231 breast cancer cells were established. Reverse transcription-polymerase chain reaction and western blotting were performed to evaluate nicotine receptor expression. To verify the functional role and underlying signaling mechanism of nicotine receptor expression induced by EBV infection, morphologic analysis, and proliferation and inhibition assays were performed., Results: Both EBV infection and LMP1 transfection increased cell proliferation and induced the up-regulation of α9-nAChR expression. Additionally, nicotine treatment induced tumorigenic activity in both EBV-infected and LMP1-transfected MDA-MB-231 breast cancer cells. Western blot and inhibitor assays showed that the nicotine-induced signaling was mediated through MAPK/ERK and AKT signaling pathways in EBV-infected and LMP1-transfected breast cancer cells, respectively., Conclusion: These results suggest that EBV infection and EBV-related LMP1 may act as potential molecular targets for breast cancer risk associated with nicotine, and provide a novel insight into the mechanism of nicotine stimulation in EBV-positive breast cancer cells., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The caudal nucleus of the solitary tract (NTS) serves as the site of the first synapse for visceral sensory inputs to the central nervous system. The NTS sends functional projections to multiple brain nuclei, with gastric-related projections primarily targeting the dorsal motor nucleus of the vagus (DMV). Previous studies have demonstrated that the majority of caudal NTS neurons that project to the DMV respond robustly to nicotine and express nicotinic acetylcholine receptors (nAChRs). However, the cytochemical identity and relationship with specific viscera of DMV-projecting, nicotine-responsive caudal NTS neurons have not been determined. The present study used transgenic mice that express enhanced green fluorescent protein (EGFP) under a GAD67 promoter in a subset of GABAergic neurons, in vivo retrograde pseudorabies viral labeling to identify gastric-related vagal complex neurons, and patch-clamp electrophysiology in acute brain stem slices to test the hypothesis that gastric-related and GABAergic inhibitory synaptic input to the DMV from the caudal NTS is under a robust modulatory control by nAChRs. Our results suggest that activation of nAChRs in the caudal NTS, but not DMV, potentiates GABAergic, but not glutamatergic, input to the DMV. Gastric-related caudal NTS and DMV neurons are directly involved in this nicotine-sensitive circuitry. Understanding the central patterns of nicotinic modulation of visceral sensory-motor circuitry may help develop therapeutic interventions to restore autonomic homeostasis in patients with autonomic impairments., (Copyright © 2015 the American Physiological Society.)

The article focuses on a study which investigated the effects of synthetic cannabinoid WIN55, 212-2 on nicotine-activated currents (Inic) in rat trigeminal ganglion through the use of whole-cell patch clamp techniques. The association of cannabinoid and nicotinic acetylcholine receptors with algesia is mentioned. The study concludes that nicotine receptors can be plugged from outside the membrane by drugs containing WIN55, 212-2.