5-Hydroxytryptamine in the Carotid Body of the Cat

Chemoreceptors for oxygen reside within the carotid body, but it is not known which cells actually sense hypoxia and by what mechanisms they transduce this information into afferent signals in the carotid sinus nerve. We have developed systems for the growth of glomus cells of the carotid body in dissociated cell culture. Here we demonstrate that, as in vivo, these cells contain the putative neurotransmitters dopamine, serotonin, and norepinephrine. Oxygen tension regulates the rate of dopamine secretion from the glomus cells. Similar to chemically stimulated catecholamine secretion from other adrenergic cells this hypoxia-stimulated release requires extracellular calcium. These results are compatible with the suggestion that the glomus cells of the carotid body are chemoreceptor cells and that they signal hypoxia by regulated secretion of dopamine.Since the work of Heymans (1) it has been known that the hypoxic ventilatory drive originates primarily within the carotid body. Subsequent work has outlined the role of this sensory organ in control of breathing at sea level and at higher altitude (1, 2) and in the sensation of dyspnea (3). However, definition of the molecular basis of oxygen transduction has been hampered by the complexity of the carotid body. It contains several cell types, including endothelial, sustentacular, and glomus cells as well as the terminals of afferent and sympathetic nerves (4, 5), but it is not known which are actually capable of sensing the level of oxygen. The glomus cells have been attractive candidates to be chemoreceptor cells because they contain dopamine, a transmitter secreted from the carotid body during hypoxia, and because they form morphological synapses with afferent nerve terminals (5, 6). We have designed systems for the growth of glomus cells in culture in order to investigate the neurophysiology of these cells and their potential role in chemoreception (7). Here, we report evidence that carotid body glomus cells in culture synthesize and secrete putative neurotransmitters and manifest chemosensitivity in their control of dopamine secretion. MATERIALS AND METHODSDissociated newborn rat carotid body cells were cultured as described (7) in 24-well plates and were grown in a humidified atmosphere of Po2 151 mm Hg, Pco2 36 mm Hg in supplemented F-12 medium (pH 7.2). Nerve growth factor was not added to the medium. Enrichment for glomus cells could be achieved by the use of tyrosine-free medium (7), but successful elimination of other cells required several weeks of growth under these conditions. Since the very few cells in the carotid body was the limiting factor in the number of experiments that were possible and since there was a slow but noticeable decrement in catecholamine content in cultures >7-10 days old, we elected not to use this long-term enrichment procedure. Hypoxic conditions were identical except that the Po2 was diminished to 36 mm Hg. Since there are only a few thousand cells in the carotid body, each experiment necessitated the pooling of dissocia...

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“…Glomus cells in vivo contain several putative neurotransmitters, including norepinephrine , dopamine, and serotonin (5,10). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Oxygen chemoreception by carotid body cells in culture.

Fishman¹,

Greene²,

Platika³

1985

Proc. Natl. Acad. Sci. U.S.A.

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“…The inhibition evoked by dopamine was reduced during SP infusions whereas that associated with 5-HT was potentiated. It was not possible to determine what was responsible for these effects, nor what effect SP was having on the release of dopamine or 5-HT, both of which are present in the carotid body (Chiocchio, Biscardi & Tramezzani, 1967;Chiocchio, King, Carballo & Angelacos, 1971). It has been shown in cats that intra-nigral SP results in an increased release of dopamine (Ch6ramy, Niedullon, Michelot & Glowinski, 1977) and, in rats, that SP injected into the lateral ventricles stimulates the synthesis and utilization of dopamine and 5-HT in brain (Carlsson, Magnusson, Fisher, Chang & Folkers, 1977).…”

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confidence: 99%

Effects of substance P on carotid chemoreceptor activity in the cat.

McQueen¹

1980

The Journal of Physiology

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SUMMARY1. The influence of substance P (SP) on spontaneous chemosensory discharge and on responses of the carotid chemoreceptors to various drugs has been investigated in pentobarbitone anaesthetized cats in which chemoreceptor activity was recorded from the peripheral end of a sectioned sinus nerve.2. After an initial slight inhibition during the first 5-15 see following the injection, SP (0.1-100 j#g I.A.) caused a dose-related increase in discharge which lasted for 45-300 see in artificially ventilated cats, discharge being increased by about 50 % on average. The increase was of shorter duration when the animals were allowed to breathe spontaneously. 3. The delayed increase in discharge was not secondary to the hypotension caused by SP, nor was it entirely due to changes in bronchomotor tone resulting from direct or indirect actions of SP, although such changes contributed to the response. It was not possible to determine whether the excitation was due to a direct effect of SP on the chemoreceptors.4. Chemosensory excitation evoked by NaCN (5 ,ag I.A.) was potentiated during I.A. infusions of SP and also 10-20 min after SP (10 jagtl.A.) had been injected. In contrast, responses to ACh (50 jag I.A.) were inhibited. These effects may be due to a nicotinic-blocking action of SP on the carotid chemoreceptors. It was also found that the inhibitory action of dopamine (5 jag I.A.) was reduced during SP infusion whereas that of 5-HT (10 jag I.A.) was potentiated.5. A sample of crude SP had effects on spontaneous chemoreceptor discharge and responses to NaCN and ACh which were qualitatively similar to those obtained using synthetic SP.6. The physiological significance of the results is discussed and it is concluded that the interpretation depends upon whether or not SP is present in the cat's carotid body.

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“…Some authors have indicated that catecholamines may not have a significant role in chemoreceptor function (Eyzaguirre & Koyano, 1965;Eyzaguirre & Zapata, 1968;Zapata et al, 1969), although other evidence indicates otherwise (Biscoe, 1965;Sampson, 1972;Andrew, Black, Comroe & Jacobs, 1972). A physiological role for 5-hydroxytryptamine (5-HT) may not be discarded, since the carotid body contains a certain amount of 5-HT (Chiocchio et al, 1967(Chiocchio et al, , 1971; furthermore, histochemical methods have shown that 5-HT is located in the electron-dense core vesicles of the Type I cells (Chiocchio et al, 1967;I-Li Chen et al, 1967). These findings lend some support to the view that 5-HT may have some functional role in the carotid body.…”

Section: Introductionmentioning

confidence: 99%

“…A physiological role for 5-hydroxytryptamine (5-HT) may not be discarded, since the carotid body contains a certain amount of 5-HT (Chiocchio et al, 1967(Chiocchio et al, , 1971; furthermore, histochemical methods have shown that 5-HT is located in the electron-dense core vesicles of the Type I cells (Chiocchio et al, 1967;I-Li Chen et al, 1967). These findings lend some support to the view that 5-HT may have some functional role in the carotid body.…”

Section: Introductionmentioning

confidence: 99%

The Action of 5‐hydroxytryptamine on Chemoreceptor Discharges of the Cats Carotid Body

Nishi

1975

British J Pharmacology

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1 Chemoreceptor discharges were recorded in vivo from fine filaments of the carotid sinus nerve containing a single or several active units; their frequency was used as an index of receptor activity. The effects of 5-hydroxytryptamine (5-HT) on chemoreceptors were studied in 26 adult cats. At times, sinus baroreceptor discharges were recorded from the carotid nerve and the effect of 5-HT on the discharges was examined.2 Intra-carotid injections of 5-HT (2-20 jg) induced a sharp and brief increase in chemoreceptor discharges, followed by depression or block which lasted for several seconds. Repeated injections at short intervals, and a small dose after a large dose of 5-HT resulted in depressed or blocked response to 5-HT. 3 5-HT in high doses (10-20,g, i.a.) slightly depressed the chemoreceptor discharges induced by either acetylcholine (ACh) or NaCN, when these substances were applied within 20 s after 5-HT. 5-HT (5-20,ug, i.a.) applied during asphyxia induced a further increase in chemoreceptor discharges, soon followed by block of the discharges lasting for several seconds. 4 Atropine or hexamethonium in high doses did not change the chemoreceptor response to 5-HT, while that to ACh was markedly depressed. 5 (+)-Lysergic diethylamide (LSD), methysergide or gramine did not alter the response to 5-HT, while LSD in low doses produced a marked increase in chemoreceptor discharges.. 6 Acute and chronic treatment with reserpine (5-10 mg/kg, i.v.) of the animals did not change the sensitivity and the reactivity of the chemoreceptor to ACh and NaCN, while the chemoreceptor response to 5-HT was augmented, indicating an increase in the sensitivity of chemoreceptors to 5-HT. 7 5-HT in small doses (2-10 Mig, i.a.) induced a marked increase in sinus baroreceptor discharges; subsequently discharges were depressed or blocked for several seconds. 8 The results are discussed in relation to possible mechanism of action of 5-HT on the chemoreceptors. It is concluded that the exogenous 5-HT probably acts directly on the chemosensory nerve endings and depolarizes them, but 5-HT contained in the carotid body does not play a significant role in the generation of chemoreceptor discharges.

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5-Hydroxytryptamine in the Carotid Body of the Cat

Abstract: Glomus cells, at least in the carotid body of cats, contain catechol and indolamines. Cells containing adrenaline, noradrenaline, and 5-hydroxytryptamine were identified.

Cited by 63 publications

References 8 publications

Oxygen chemoreception by carotid body cells in culture.

Oxygen chemoreception by carotid body cells in culture.

Effects of substance P on carotid chemoreceptor activity in the cat.

The Action of 5‐hydroxytryptamine on Chemoreceptor Discharges of the Cats Carotid Body

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