Thyroid status affects 5-HT<sub>2A</sub>receptor modulation of breathing before, during, and following exposure of hamsters to acute intermittent hypoxia

Varney, Abrea A.; Schlenker, Evelyn H.

doi:10.1152/ajpregu.00495.2007

Cited by 9 publications

(7 citation statements)

References 52 publications

(63 reference statements)

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“…In some cases thyroid hormone therapy reverses these dysfunctions, but not always (Jha et al, 2006; Misiolek et al, 2007). At the molecular level, thyroid hormones affect the expression and phosphorylation of various enzymes and the expression of pumps, channels and neurotransmitter systems that may affect ventilation including opioids, serotonin, gamma amino butyric acid, and dopamine (Burton and Kazemi, 2000; Diez et al, 2008; Kulikov and Zubkov, 2007; Sarkar et al, 2006; Schlenker, 1994; Slotkin and Slepetis, 1984; Varney and Schlenker, 2007). …”

Section: Introductionmentioning

confidence: 99%

Hypothyroidism stimulates D2 receptor-mediated breathing in response to acute hypoxia and alters D2 receptors levels in carotid bodies and brain

Schlenker

Schultz

2012

Respiratory Physiology & Neurobiology

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Hypothyroidism can depress breathing and alter dopamine D2 receptor expression and function. We hypothesized that relative to euthyroid hamsters (EH), hypothyroid hamsters (HH) contain increased D2 receptors in brain regions associated with breathing and carotid bodies (CB), and that stimulation of D2 receptors would decease ventilation more in the HH compared to the EH. Hamsters were treated with vehicle, carmoxirile (peripherally acting D2 receptor agonist), or bromocriptine (central and peripherally acting D2 receptor agonist) and breathing was evaluated during exposure to air, hypoxia, and then air. HH exhibited increased D2 receptor protein levels in the striatum and CB’s, but decreased levels in the paraventricular hypothalamic nucleus. Relative to vehicle, carmoxirole and bromocriptine stimulated ventilation in the HH during and following exposure to hypoxia. Only bromocriptine depressed ventilation in the EH during and after exposure to hypoxia. Thus,, hypothyroidism impacts the expression of D2 receptors in the carotid body, PVN and striatum, and D2 stimulation affects ventilation remarkably differently than in EH.

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Section: Introductionmentioning

confidence: 99%

Hypothyroidism stimulates D2 receptor-mediated breathing in response to acute hypoxia and alters D2 receptors levels in carotid bodies and brain

Schlenker

Schultz

2012

Respiratory Physiology & Neurobiology

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“…The advantage of using an agent such as PTU is that it can be administered in drinking water at various concentrations that may induce different levels of hypothyroidism (Goodman and Gilbert, 2007). Moreover, this is a method that has been used previously in our laboratory in hamsters (Varney and Schlenker, 2007). …”

Section: Introductionmentioning

confidence: 99%

“…For example, Schlenker and coworkers showed PTU-induced hypothyroidism in hamsters depressed the stimulatory effects of naloxone, a mu-opioid receptor antagonist, on ventilation (Schlenker, 1994). More recently, Varney and Schlenker reported that a specific serotonin 2A receptor antagonist (R)-(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (MDL 100907) resulted in long-term depression of ventilation (a decrease in ventilation following intermittent hypoxia relative to baseline values) in euthyroid, but not in hypothyroid hamsters (Varney and Schlenker, 2007). …”

Section: Introductionmentioning

confidence: 99%

Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases d1 receptor expression in carotid bodies, PVN and striatum of hamsters

Schlenker

Schultz

2011

Brain Research

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Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)–induced hypothyroidism in hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for three months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390, a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O2 in N2), hypoxic (10% O2 in N2) and hypercapnic (5% CO2 in O2) air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH 23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH 23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH.

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“…Hypothyroidism also affects the respiratory system and control of breathing (Duranti et al, 1993) and (see references (Schlenker, 2012; Schlenker et al, 1994)). Several studies from our laboratory indicate that hypothyroidism specifically affects modulation of breathing by altering the function of various neurotransmitter systems and receptors including opioids, serotonin and dopamine (Schlenker et al, 1994; Schlenker and Schultz, 2011a; Varney and Schlenker, 2007). …”

Section: 0 Introductionmentioning

confidence: 99%

In adult female hamsters hypothyroidism stimulates D1 receptor-mediated breathing without altering D1 receptor expression

Schlenker¹,

Rio²,

Schultz³

2015

Respiratory Physiology & Neurobiology

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Hypothyroidism affects cardiopulmonary regulation and function of dopaminergic receptors. Here we evaluated effects of 5 months of hypothyroidism on dopamine D1 receptor modulation of breathing in female hamsters using a D1 receptor antagonist SCH23390. Euthyroid hamsters (EH) served as controls. Results indicated that hypothyroid female hamsters (HH) exhibited decreased body weights and minute ventilation (VE) following hypoxia due to decreased frequency of breathing (F). Moreover, SCH 23390 administration in HH increased VE by increasing tidal volume during exposure to air, hypoxia and following hypoxia. Relative to vehicle, SCH 23390 treatment decreased body temperature and hypoxic VE responsiveness in both groups. In EH, SCH 23390 decreased F in air, hypoxia and post hypoxia, and VE during hypoxia trended to decrease (P=0.053). Finally, expression of D1 receptor protein was not different between the two groups in any region evaluated. Thus, hypothyroidism in older female hamsters affected D1 receptor modulation of ventilation differently relative to euthyroid animals, but not expression of D1 receptors.

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Thyroid status affects 5-HT_2Areceptor modulation of breathing before, during, and following exposure of hamsters to acute intermittent hypoxia

Abstract: Varney AA, Schlenker EH. Thyroid status affects 5-HT2A receptor modulation of breathing before, during, and following exposure of hamsters to acute intermittent hypoxia.

Cited by 9 publications

References 52 publications

Hypothyroidism stimulates D2 receptor-mediated breathing in response to acute hypoxia and alters D2 receptors levels in carotid bodies and brain

Hypothyroidism stimulates D2 receptor-mediated breathing in response to acute hypoxia and alters D2 receptors levels in carotid bodies and brain

Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases d1 receptor expression in carotid bodies, PVN and striatum of hamsters

In adult female hamsters hypothyroidism stimulates D1 receptor-mediated breathing without altering D1 receptor expression

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Thyroid status affects 5-HT2Areceptor modulation of breathing before, during, and following exposure of hamsters to acute intermittent hypoxia

Abstract: Varney AA, Schlenker EH. Thyroid status affects 5-HT2A receptor modulation of breathing before, during, and following exposure of hamsters to acute intermittent hypoxia.

Cited by 9 publications

References 52 publications

Hypothyroidism stimulates D2 receptor-mediated breathing in response to acute hypoxia and alters D2 receptors levels in carotid bodies and brain

Hypothyroidism stimulates D2 receptor-mediated breathing in response to acute hypoxia and alters D2 receptors levels in carotid bodies and brain

Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases d1 receptor expression in carotid bodies, PVN and striatum of hamsters

In adult female hamsters hypothyroidism stimulates D1 receptor-mediated breathing without altering D1 receptor expression

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Thyroid status affects 5-HT_2Areceptor modulation of breathing before, during, and following exposure of hamsters to acute intermittent hypoxia