Changes in carotid body amine levels and effects of dopamine on respiration in rats treated neonatally with capsaicin

McQueen, Daniel S.; Mir, Anis K.

doi:10.1111/j.1476-5381.1984.tb16531.x

Cited by 9 publications

(4 citation statements)

References 25 publications

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“…Taken with the other in vivo studies presented here (CSNX and CAP studies) it seems that hypoxia may release L-CSNO from PGCs that in turn activate small diameter unmyelinated C-fiber chemoafferents to mediate the HVR. The hypoxic ventilatory responses recorded in this study are consistent with evidence that the ventilatory responses to hypoxic gas challenges are largely abolished in adult rats with CSNX ( Getsy et al, 2020 ; 2021a ) and adult rats treated with capsaicin as neonates ( McQueen and Mir, 1984 ; De Sanctis et al, 1991 ). Our data that the ventilatory responses elicited by L-CSNO and L-GSNO are markedly diminished in CSNX and CAP rats greatly expands our understanding of the pharmacology of these endogenous S-nitrosothiols.…”

Section: Discussionsupporting

confidence: 87%

Hypoxia releases S-nitrosocysteine from carotid body glomus cells—relevance to expression of the hypoxic ventilatory response

Seckler,

Getsy,

May

et al. 2023

Front. Pharmacol.

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We have provided indirect pharmacological evidence that hypoxia may trigger release of the S-nitrosothiol, S-nitroso-L-cysteine (L-CSNO), from primary carotid body glomus cells (PGCs) of rats that then activates chemosensory afferents of the carotid sinus nerve to elicit the hypoxic ventilatory response (HVR). The objective of this study was to provide direct evidence, using our capacitive S-nitrosothiol sensor, that L-CSNO is stored and released from PGCs extracted from male Sprague Dawley rat carotid bodies, and thus further pharmacological evidence for the role of S-nitrosothiols in mediating the HVR. Key findings of this study were that 1) lysates of PGCs contained an S-nitrosothiol with physico-chemical properties similar to L-CSNO rather than S-nitroso-L-glutathione (L-GSNO), 2) exposure of PGCs to a hypoxic challenge caused a significant increase in S-nitrosothiol concentrations in the perfusate to levels approaching 100 fM via mechanisms that required extracellular Ca2+, 3) the dose-dependent increases in minute ventilation elicited by arterial injections of L-CSNO and L-GSNO were likely due to activation of small diameter unmyelinated C-fiber carotid body chemoafferents, 4) L-CSNO, but not L-GSNO, responses were markedly reduced in rats receiving continuous infusion (10 μmol/kg/min, IV) of both S-methyl-L-cysteine (L-SMC) and S-ethyl-L-cysteine (L-SEC), 5) ventilatory responses to hypoxic gas challenge (10% O2, 90% N2) were also due to the activation of small diameter unmyelinated C-fiber carotid body chemoafferents, and 6) the HVR was markedly diminished in rats receiving L-SMC plus L-SEC. This data provides evidence that rat PGCs synthesize an S-nitrosothiol with similar properties to L-CSNO that is released in an extracellular Ca2+-dependent manner by hypoxia.

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Section: Discussionsupporting

confidence: 87%

Hypoxia releases S-nitrosocysteine from carotid body glomus cells—relevance to expression of the hypoxic ventilatory response

Seckler,

Getsy,

May

et al. 2023

Front. Pharmacol.

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“…The mean ID50 for DA (103 + 30 (±S.E., n = 8) nmol kg-') was not significantly different from the value (74 + 14, n = 8) obtained under pentobarbitone anaesthesia by McQueen & Mir (1984), and was increased to > 2000 nmol kg-' after domperidone (100 ,ug kg-' i.v. ), indicating substantial blockade of D2 receptors.…”

mentioning

confidence: 86%

“…Using previously described methods (McQueen & Mir, 1984), respiratory responses to hypoxia (breathing 10% 02) and DA (i.v.) were obtained before and after administering the DA D2 receptor antagonist domperidone (which blocks DA-induced chemoinhibition - McQueen & Mir, 1984) in rats anaesthetized with halothane (1 % in air).…”

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confidence: 99%

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Proceedings of the Physiological Society, 28‐29 March 1985, University College London Meeting: Communications

1985

The Journal of Physiology

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We have previously shown that the Lambert-Eaton myasthenic syndrome (L.E.M.S.) is an autoimmune disorder (Lang, Newsom-Davis, Prior & Wray, 1983). IgG autoantibodies interfere with release of acetylcholine from presynaptic nerve terminals of the skeletal neuromuscular junction. The experiments reported here were designed to investigate the mechanism of action of these antibodies at depolarized nerve terminals.Mice were injected with control or L.E.M.S. IgG (30 mg/day, i.P.) for 2 days, and the diaphragm muscle removed on the third day, as previously described (Lang et al. 1983). Miniature end-plate potentials (m.e.p.p.s) were recorded using microelectrodes in Krebs solution (23-26 'C) containing high K+ concentration (15-9 mM) and a range of Ca2+ concentrations (0-25-2-5 mm).In controls, m.e.p.p. frequency increased with Ca2+ concentration from a value of 5 03 + 0 69 s-1 (n = 19 end-plates) at 0-25 mM-Ca2+ concentration to a plateau value of 79-3 + 6-8 s-1 (n = 18) at 1-5 mM-Ca2+ concentration. Further increase in Ca2+ concentration produced no further increase in this plateau value. The curve of m.e.p.p. frequency versus Ca2+ concentration for L.E.M.S. IgG-treated animals was similar in shape to that for controls, but with significantly reduced (P < 0-002) m.e.p.p. frequency values at all Ca2+ concentrations. The extent of these reductions was to 34 46 % of control values. Thus the curve was shifted to the right with a reduced plateau. The plateau value of m.e.p.p. frequency was reached at similar Ca2+ concentrations as for controls but was reduced to 36-4 + 4-9 s51 (n = 19, Ca2+ concentration = 1-5 mM).These reductions in m.e.p.p. frequency at potassium-depolarized nerve terminals by L.E.M.S. IgG indicate that it is unlikely that this antibody acts solely (if at all) on action potential mechanisms, since no action potentials were involved in the present experiments. On the other hand, voltage-dependent Ca2+ channels would be expected to be opened by the depolarization produced under the above experimental conditions. L.E.M.S. IgG may act on these latter channels to cause their loss of function as suggested previously (Lang, Newsom-Davis, Prior & Wray, 1984). The present results are consistent with such an action, and the reduced plateau value of the above curve produced by the L.E.M.S. IgG shows further that the mechanism is not one of competitive antagonism.

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Localization of Dopamine D2 Receptor mRNA in the Rabbit Carotid Body and Petrosal Ganglion by in situ Hybridization

Schamel

Verna

1993

Advances in Experimental Medicine and Biology

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Changes in carotid body amine levels and effects of dopamine on respiration in rats treated neonatally with capsaicin

Cited by 9 publications

References 25 publications

Hypoxia releases S-nitrosocysteine from carotid body glomus cells—relevance to expression of the hypoxic ventilatory response

Hypoxia releases S-nitrosocysteine from carotid body glomus cells—relevance to expression of the hypoxic ventilatory response

Proceedings of the Physiological Society, 28‐29 March 1985, University College London Meeting: Communications

Localization of Dopamine D2 Receptor mRNA in the Rabbit Carotid Body and Petrosal Ganglion by in situ Hybridization

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