Catecholamine synthesis in rabbit carotid body in vitro

Central and peripheral neurons as well as neuroendocrine cells express a variety of neurotransmitters/modulators that play critical roles in regulation of physiological systems. The synthesis of several neurotransmitters/ modulators is regulated by O2-requiring rate-limiting enzymes. Consequently, hypoxia resulting from perturbations in O2 homeostasis can affect neuronal functions by altering neurotransmitter synthesis. Two broad categories of hypoxia are frequently encountered: continuous hypoxia (CH) and intermittent hypoxia (IH). CH is often seen during high altitude sojourns, whereas IH is experienced in sleep-disordered breathing with recurrent apneas (i.e., brief, repetitive cessations of breathing). This article presents what is currently known on the effects of both forms of hypoxia on neurotransmitter levels and neurotransmitter synthesizing enzymes in the central and peripheral nervous systems. biogenic amines; bioactive peptides; glutamate; ␥-amino butyric acid; gasotransmitters THE MAMMALIAN BRAIN represents 2% of the total body weight and consumes 20% of the total body oxygen for its normal function (108). This high level of oxygen consumption makes the brain an extremely sensitive tissue to changes in arterial blood oxygen levels. Many physiological systems are regulated by the nervous system, and neurotransmitters are critical for neuronal function. The rate-limiting enzymes associated with the synthesis of several neurotransmitters require molecular oxygen for their activity. Consequently, hypoxia (i.e., reduced oxygen availability) resulting from perturbations in O 2 homeostasis can profoundly impact neurotransmitter synthesis resulting in altered neuronal functions and consequently impact physiological systems.Hypoxia is experienced in a variety of physiological and pathological conditions. Two broad categories of hypoxia are most frequently encountered; continuous hypoxia (CH) and intermittent hypoxia (IH). For instance, CH is experienced by healthy humans during high altitude sojourns, whereas IH is encountered during sleep-disordered breathing with recurrent apneas; i.e., brief repetitive cessations of breathing wherein each episode lasts for tens of seconds. The purpose of this article is to provide a brief review of the effects of both forms of hypoxia on neurotransmitter levels, rate-limiting enzymes associated with neurotransmitter synthesis and the underlying mechanisms. Several of these molecules, which function as transmitters/modulators in the nervous system, are also expressed in nonneuronal tissues. However, because of space constraints, this review will focus on the effects of hypoxia on neurotransmitters in the central and peripheral nervous systems.Based on the chemical properties, neurotransmitters are divided into various groups as shown in Table 1. This review focuses on the impact of CH and IH on the synthesis of biogenic amines, acetylcholine, excitatory and inhibitory amino acids, bioactive peptides, and gasotransmitters (for examples see Table 1). BIOGENIC AMINESBiogenic ...

mentioning

confidence: 75%

Hypoxia. 3. Hypoxia and neurotransmitter synthesis

Kumar

2011

“…General procedures for the synthesis experiments have been described in previous publications (15,50). Analytic procedures have been described in detail in Conde et al (11).…”

Section: Animals and Anesthesiamentioning

confidence: 99%

Effects of low glucose on carotid body chemoreceptor cell activity studied in cultures of intact organs and in dissociated cells

Gallego-Martín

Fernandez-Martinez

Rigual

et al. 2012

The participation of the carotid body (CB) in glucose homeostasis and evidence obtained in simplified cultured CB slices or dissociated cells have led to the proposal that CB chemoreceptor cells are glucoreceptors. However, data generated in intact, freshly excised organs deny CB chemoreceptor cells' glucosensing properties. The physiological significance of the contention has prompted the present study, performed in a newly developed preparation of the intact CB organ in culture that maintains chemoreceptor cells' microenvironment. Chemoreceptor cells of intact CBs in culture retained their capacity to store, synthesize, and secrete catecholamine in response to hypoxia for at least 6 days. Aglycemia did not elicit neurosecretion in dissociated chemoreceptor cells or in intact CB in culture, but potentiated hypoxia-elicited neurosecretion, exclusively, in 1-day-old intact CB cultures and dissociated chemoreceptor cells cultured for 24 h. In fura 2-loaded cells, aglycemia (but not 1 mM) caused a slow Ca(2+)-dependent and nifedipine-insensitive increase in fluorescence at 340- to 380-nm wavelength emission ratio and augmented the fluorescent signal elicited by hypoxia. Association of nifedipine and KBR7943 (a Na(+)/Ca(2+) exchanger inhibitor) completely abolished the aglycemic Ca(2+) response. We conclude that chemoreceptor cells are not sensitive to hypoglycemia. We hypothesize that cultured chemoreceptor cells become transiently more dependent on glycolysis. Consequently, aglycemia would partially inhibit the Na(+)/K(+) pump, causing an increase in intracellular Na(+) concentration, and a reversal of Na(+)/Ca(2+) exchanger. This would slowly increase intracellular Ca(2+) concentration and cause the potentiation of the hypoxic responses. We discuss the nature of the signals detected by chemoreceptor cells for the CB to achieve its glycemic homeostatic role.

“…In the present work we have tested the capacity of a diverse group of oxidant agents to modify CB chemoreceptor cell activity, assessed by their ability to alter the normoxic and hypoxic release of catecholamines (CA), one of the most abundant chemoreceptor cell neurotransmitters. We have chosen the release of CA as an index of chemoreceptor cell activity because a tight correlation between CA release and intensity of stimulation has been well documented (10,33,43). Oxidant agents studied pertained to three different functional groups: 1) p-chloro-mercuri-phenyl-sulfonate (PCMBS) and 6,6Ј-dithiodinicotinic acid (DTNA) are nonpermeating through plasma cell membranes, and therefore their actions would be restricted to the extracellular face of the plasma membrane; 2) GSSG, 2,2Ј-dithiodipyridine (DTDP), and diamide (Dia) are permeating to cell membranes, and therefore they would cause oxidations both extracellularly and intracellularly; and 3) buthionine sulfoximine (BSO, inhibitor of the glutathione synthesis), 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, inhibitor of glutathione reductase), and 3-aminotriazole (AT, inhibitor of catalase); inhibitors of ROS disposal enzymes would cause primarily (or exclusively) intracellular oxidation.…”

mentioning

confidence: 99%

General redox environment and carotid body chemoreceptor function

Agapito

Sanz-Alfayate²,

Gomez-Niño³

et al. 2009

Carotid body (CB) chemoreceptor cells detect physiological levels of hypoxia and generate a hyperventilation, homeostatic in nature, aimed to minimize the deleterious effects of hypoxia. Intimate mechanisms involved in oxygen sensing in chemoreceptor cells remain largely unknown, but reactive oxygen species (ROS) had been proposed as mediators of this process. We have determined glutathione levels and calculated glutathione redox potential (E(GSH); indicator of the general redox environment of cells) in rat diaphragms incubated in the presence of oxidizing agents of two types: nonpermeating and permeating through cell membranes; in the latter group, unspecific oxidants and inhibitors of ROS-disposing enzymes were used. Selected concentrations of oxidizing agents were tested for their ability to modify the normoxic and hypoxic activity of chemoreceptor cells measured in vitro as their rate of release of neurotransmitters. Results evidence variable relationships between E(GSH) and the activity of chemoreceptor cells. The independence of chemoreceptor cell activity from the E(GSH) would imply that the ability of the CB to play its homeostatic role is largely preserved in any pathological or toxicological contingency causing oxidative stress. Consistent with this suggestion, it was also found that CB-mediated hypoxic hyperventilation was not altered by treatment of intact animals with agents that markedly decreased the E(GSH) in all tissues assayed.