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Carbon Monoxide — From Tool to Neurotransmitter
Published in David G. Penney, Carbon Monoxide, 2019
Nanduri R. Prabhakar, Robert S. Fitzgerald
Further evidence that CO is a transmitter in the central nervous system came from electrophysiological studies using inhibitors of HO and exogenous application of CO. Neurons in the nucleus of the solitary tract (nTS) integrate various afferent inputs arising from the cardiorespiratory systems. Glutamate is the principle excitatory transmitter (Leone and Gordon, 1989; McKitrick and Calaresu, 1989; Meely et al., 1989) and its actions are mediated by iono- and metabotropic glutamergic receptors. Glutamergic metaboreceptors have been implicated in integration of vagal sensory inputs in nTS and mediate baroreceptor reflexes (Glaum and Miller, 1992, 1993a). The synaptic effects of metaboreceptor activation can be mimicked by cGMP and are associated with activation of guanylate cyclase (Lewis et al., 1991). Because the effects of NO are coupled to cGMP, it was thought that NO is the mediator of metaboreceptor activation in nTS. However, the effects of activation of metaboreceptors was not mimicked by NO-generating substances (Glaum and Miller, 1993), and the distribution of NO-synthase did not coincide with guanalyte cyclase localization in nTS (Lin and McGrath, 1989). On the other hand, the distribution of HO-2 did coincide with the localization of guanalyte cyclase (Verma et al., 1993). Using the isolated brain slice preparation from rats (Glaum and Miller, 1993b), examined the role of CO in metaboreceptor activation in nTS. These authors tested the effects of (lS,3R)-l-aminocyclopentane-l,3-dicarboxylic acid (1S,3R)-ACPD), an agonist for glutamergic metaboreceptors, on synaptic activity in the dorsomedial subdivision of the nTS. ZnPP-9, an inhibitor of HO-2, but not the nitric oxide synthase inhibitor L-w-nitroarginine, attenuated the monosynaptic excitatory postsynaptic currents (EPSCs) evoked by (1S,3R)-ACPD. Moreover, the effects of ZnPP-9 seem to be selective because a relatively inactive analog, CuPP-9 (Drummond and Kappas, 1981), failed to attenuate the effects of (ls,3R)-ACPD. The effects of metaboreceptor activation could be mimicked by 8-bromo-cGMP, a membrane permeant analog of cGMP. However, ZnPP-9 had no effect on other types of glutamergic receptor activation. These results suggested that multiple metaboglutamergic receptors exist in the dorsomedial nTS and one of them is coupled to CO.
Transcutaneous auricular vagus nerve stimulation effects on inflammatory markers and clinical evolution of patients with COVID-19: a pilot randomized clinical trial
Published in Expert Review of Medical Devices, 2022
Laura Uehara, João Carlos Ferrari Corrêa, Raphael Ritti, Paulo Leite, Deivide Rafael Gomes de Faria, Kevin Pacheco-Barrios, Luis Castelo-Branco, Felipe Fregni, Fernanda Ishida Corrêa
This physiological mechanism, known as inflammatory reflex, occurs in the presence of innate immune responses and inflammation, during the invasion of pathogens and tissue injury. In this way, the afferent vagus nerve is signaled connecting with brain regions such as the solitary tract nucleus and forebrain. Consequently, the efferent vagus nerve-mediated immunoregulatory output to the spleen, liver, and gastrointestinal tract ultimately suppresses pro-inflammatory cytokines [16].