Neurochemical Aspects of Thermoregulation

Myers, R.D.; Lee, T. F.

doi:10.1007/978-3-642-74078-7_5

Cited by 27 publications

(8 citation statements)

References 199 publications

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“…α 2C -AR is present in high densities in the hippocampus, the olfactory system, the striatum, and the cerebral cortex. However, α 2A -AR is the subtype most prominent and broadly distributed, being concentrated in the cortex, autonomic centers, amygdala, septum, hippocampus, and hypothalamus [32,[34][35][36][37]. The subtype α 2A -AR also predominates in the dorsal horn, where it is largely expressed by intrinsic neurons, although an additional population is localized on the terminals of nociresponsive primary afferent fibers [32,35,[38][39][40].…”

Section: Distributionmentioning

confidence: 96%

“…Only slight selectivity for α 2C -AR with respect to the other two subtypes, α 2A -and α 2B -AR, is shown according to the potency order MK912 (105) > rauwolscine (95) = yohimbine (2) > WB 4101 (9) > prazosin (1) > corynanthine (96). Idazoxan (15), imiloxan (110), phentolamine (116), SKF 86.466 (34), and SKF 104.856 (36), instead, display the same antagonist potency at each α 2 -AR subtype.…”

Section: General Considerationmentioning

confidence: 99%

See 1 more Smart Citation

Agonists and Antagonists Targeting the Different α2-Adrenoceptor Subtypes

Gentili

Pigini²,

Piergentili³

et al. 2007

CTMC

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Chemical and biological strategies have provided evidence for alpha(2)-receptor heterogeneity, to date classified in three different subtypes, alpha(2A), alpha(2B), and alpha(2C). These are widely distributed throughout the body and mediate numerous effects; therefore, the potential therapeutic indications of agonists and antagonists are numerous. Nevertheless, the lack of subtype-selectivity of the well-known compounds represents a major limit for their use. SAR studies may help to design new and more selective drugs.

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Section: Distributionmentioning

confidence: 96%

Section: General Considerationmentioning

confidence: 99%

Agonists and Antagonists Targeting the Different α2-Adrenoceptor Subtypes

Gentili

Pigini²,

Piergentili³

et al. 2007

CTMC

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“…This is a possible mechanism for the opposite alterations in the hypothermic responses to dexmedetomidine in KO and OE mice. The preoptic area of the anterior hypothalamus is a central site of thermoregulation in rodents, but pharmacological experiments have demonstrated that nigrostriatal dopaminergic neurons also participate in the complex regulation of body temperature (33). It is also possible that the modulatory effects of ␣ 2C -ARs on body temperature are due to altered heat production by peripheral muscles, which is indirectly controlled by nigrostriatal pathways.…”

Section: Genetic Alteration Of ␣ 2c -Adrenoceptor Expression 41mentioning

confidence: 99%

Genetic Alteration of α_2C-Adrenoceptor Expression in Mice: Influence on Locomotor, Hypothermic, and Neurochemical Effects of Dexmedetomidine, a Subtype-Nonselective α₂-Adrenoceptor Agonist

et al. 1997

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SUMMARY␣ 2 -Adrenergic receptors (␣ 2 -ARs) regulate many physiological functions and are targets for clinically important antihypertensive and anesthetic agents. Three human and mouse genes encoding ␣ 2 -AR subtypes (␣ 2A , ␣ 2B , and ␣ 2C ) have been cloned. We investigated the involvement of the ␣ 2C -AR in ␣ 2 -adrenergic pharmacology by applying molecular genetic techniques to alter the expression of ␣ 2C -AR in mice. The effects of dexmedetomidine, a subtype-nonselective ␣ 2 -AR agonist, on monoamine turnover in brain and on locomotor activity were similar in mice with targeted inactivation of the ␣ 2C -AR gene and in their controls, but the hypothermic effect of the ␣ 2 -AR agonist was significantly attenuated by the receptor gene inactivation. Correspondingly, another strain of transgenic mice with 3-fold overexpression of ␣ 2C -AR in striatum and other brain regions expressing ␣ 2C -AR showed normal reductions in brain monoamine metabolism and locomotor activity after dexmedetomidine, but their hypothermic response to the ␣ 2 -AR agonist was significantly accentuated. The hypothermic effect of ␣ 2 -AR agonists thus seems to be mediated in part by ␣ 2C -AR. Some small but statistically significant differences between the strains were also noted in brain dopamine metabolism. Lack of ␣ 2C -AR expression was linked with reduced levels of homovanillic acid in brain, and mice with increased ␣ 2C -AR expression had elevated concentrations of the dopamine metabolite compared with their controls.␣ 2 -ARs mediate many physiological functions and pharmacological effects in the central nervous system, mainly by inhibiting neuronal firing and release of NE and other neurotransmitters. ␣ 2 -ARs are also involved in a wide range of functions in peripheral tissues (e.g., in the regulation of NE release from sympathetic nerves, smooth muscle contraction, platelet aggregation, insulin secretion, glomerular filtration, and energy metabolism) (1). Activation of ␣ 2 -ARs with the highly specific ␣ 2 -AR agonist dexmedetomidine results in bradycardia, hypotension, hypothermia, locomotor inhibition, anxiolysis, analgesia, sedation, and, with higher doses, anesthesia. Dexmedetomidine also reduces the turnover of the monoamine neurotransmitters NE, DA, and 5-HT (serotonin) in brain (2).Recent pharmacological and biochemical research has led to a subdivision of ␣ 2 -ARs into three distinct subtypes: ␣ 2A -, ␣ 2B -, and ␣ 2C -ARs. This classification was first based on the pharmacological properties of the receptors and was confirmed through the cloning of three distinct ␣ 2 -AR genes in humans, rats, mice, and other species (3). Each receptor has a distinct tissue distribution. In the central nervous system of the rat, ␣ 2A -ARs are widely expressed, whereas the other ␣ 2 -AR subtypes have more limited distributions. ␣ 2C -ARs are present in the basal ganglia, olfactory tubercle, hippocam-ABBREVIATIONS: AR, adrenergic receptor; DA, dopamine; NE, norepinephrine; MHPG, 3-methoxy-4-hydroxyphenylglycol; HVA, homovanillic acid; 5-HT,...

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“…Moreover, many studies which used agonists/antagonists of 5-HT, such as cyproheptadine or methysergide, were also performed in the 1980s and reviewed by Clark and Lipton 2) . According to this review, different results of Tb response were obtained after performing the same serotonergic pharmacological manipulations, and thus the authors concluded that the role of 5-HT in thermoregulation was obscure 29) . This is likely because the vast majority of experiments have been pharmacological in nature.…”

Section: History Of Research On 5-ht and Thermoregulationmentioning

confidence: 99%

Role of serotonergic system in thermoregulation in rats

Ishiwata

2014

JPFSM

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The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) is involved in the regulation of several basic physiological functions such as hormone secretion, sleep-wake cycle, motor control, immune system functioning, nociception, food intake, energy balance and thermoregulation. In addition, 5-HT participates in higher brain functions, such as cognition and emotional states, by modulating synaptic plasticity and neurogenesis. Furthermore, 5-HT has recently captured the spotlight in connection with depression, synthetic narcotic drugs, hot flash, central fatigue, etc. Regarding thermoregulation, many studies have examined the relationship between 5-HT and body temperature (Tb) regulation since the 1960s. Feldberg and Myers, in pioneering experiments, first reported that microinjection of 5-HT into the cerebral ventricles or hypothalamus induced a rise in Tb. Subsequently, research on 5-HT and regulation of Tb continued and topics in recent years include resolving of 5-HT receptor subtypes, such as 5-HT 1A , 5-HT 3 , 5-HT 7 , and pinpointing a local area or network for thermoregulation. In this short review, I first outline the serotonergic system in the brain, summarize the history of research on 5-HT and thermoregulation, and finally focus on recent research in the 21 st century.

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Neurochemical Aspects of Thermoregulation

Cited by 27 publications

References 199 publications

Agonists and Antagonists Targeting the Different α2-Adrenoceptor Subtypes

Agonists and Antagonists Targeting the Different α2-Adrenoceptor Subtypes

Genetic Alteration of α_2C-Adrenoceptor Expression in Mice: Influence on Locomotor, Hypothermic, and Neurochemical Effects of Dexmedetomidine, a Subtype-Nonselective α₂-Adrenoceptor Agonist

Role of serotonergic system in thermoregulation in rats

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Neurochemical Aspects of Thermoregulation

Cited by 27 publications

References 199 publications

Agonists and Antagonists Targeting the Different &#945;2-Adrenoceptor Subtypes

Agonists and Antagonists Targeting the Different &#945;2-Adrenoceptor Subtypes

Genetic Alteration of α2C-Adrenoceptor Expression in Mice: Influence on Locomotor, Hypothermic, and Neurochemical Effects of Dexmedetomidine, a Subtype-Nonselective α2-Adrenoceptor Agonist

Role of serotonergic system in thermoregulation in rats

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Product

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About

Agonists and Antagonists Targeting the Different α2-Adrenoceptor Subtypes

Agonists and Antagonists Targeting the Different α2-Adrenoceptor Subtypes

Genetic Alteration of α_2C-Adrenoceptor Expression in Mice: Influence on Locomotor, Hypothermic, and Neurochemical Effects of Dexmedetomidine, a Subtype-Nonselective α₂-Adrenoceptor Agonist