Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro

Chiu, Tsai-Hsien; Chen, Mei Jane; Yang, Yea Ru; Yang, Jia Jang; Tang, Feng‐Yao

doi:10.1016/0014-2999(95)00417-j

Cited by 76 publications

(63 citation statements)

References 35 publications

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“…To make the picture even more uniform, the soma-dendritic α 2 -autoreceptors of the noradrenergic locus coeruleus neurones of the rat have recently been identified as pharmacologically α 2D , i.e. genetically α 2A/D (Chiu et al 1995;Nörenberg et al 1997). The results of the present study also are in accord with the view that α 2A/D is a pair of orthologous receptors of which only one occurs in a given species.…”

Section: Subclassification Of α 2 -Autoreceptorssupporting

confidence: 80%

A re-investigation of questionable subclassifications of presynaptic α2-autoreceptors: rat vena cava, rat atria, human kidney and guinea-pig urethra

Trendelenburg

Sutej

Wahl

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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It has been suggested that at least the majority of mammalian presynaptic alpha2-autoreceptors belong to the genetic alpha2A/D-adrenoceptor subtype. The aim of the present study was to re-examine the alpha2-autoreceptors in tissues in which previous assignments conflicted with this alpha2A/D rule: in the rat vena cava and rat heart atria, where the autoreceptors were classified as alpha2B or similar to, but not identical with, alpha2D, and in the human kidney, where they were classified as alpha2C. Also re-examined were the autoreceptors in the guinea-pig urethra, where they were suggested to be alpha2A, in agreement with the rule, but in contrast to indications that the alpha2A/D-adrenoceptor of the guinea pig possesses alpha2D pharmacological properties. Tissue pieces were preincubated with 3H-noradrenaline and then superfused and stimulated electrically under autoinhibition-free or almost autoinhibition-free conditions. The Kd values of up to 14 antagonists (including the partial agonist oxymetazoline) against the release-inhibiting effect of the alpha2 agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) were determined. UK 14,304 reduced the evoked overflow of tritium with an EC50 between 6.3 and 13.2 nM. All antagonists (except prazosin in one case) shifted the concentration-inhibition curve of UK 14,304 to the right. Comparison of the Kd values thus obtained with Kd values at known alpha2 subtypes indicated that the autoreceptors in the rat vena cava, rat atria and the guinea-pig urethra were alpha2D and those in the human kidney alpha2A. For example, the pKd values of the antagonists in the rat vena cava, in rat atria and in the guinea-pig urethra were closely correlated with pKd values at the prototypic alpha2D radioligand binding sites in the bovine pineal gland (r = 0.96, P < 0.001; r = 0.92, P < 0.01; and r = 0.95; P < 0.001) and with the pKd values at the alpha2D-autoreceptors of guinea-pig atria (r = 0.99, P < 0.001; r = 0.95, P < 0.001; and r = 0.98, P < 0.001). The pKd values at the autoreceptors in rat vena cava, rat atria and guinea-pig urethra were not significantly or more loosely correlated with pKd values at alpha2A, alpha2B and alpha2C binding sites and alpha2A-autoreceptors. On the other hand, the pKd values of the antagonists in the human kidney were closely correlated with pKd values at the prototypic alpha2A radioligand binding sites in HT29 cells (r = 0.95; P < 0.001) and with pKd values at the alpha2A-autoreceptors of the pig brain cortex (r = 0.97; P < 0.001), but were not significantly or more loosely correlated with pKd values at alpha2B, alpha2C and alpha2D binding sites and alpha2D-autoreceptors. In contrast to previous suggestions, the autoreceptors in rat vena cava and atria are alpha2D, those in the human kidney alpha2A, and those in the guinea-pig urethra equally alpha2D. All, therefore, conform to the rule that alpha2-autoreceptors belong at least predominantly to the genetic alpha2A/D subtype of the alpha2-adrenoceptor. The apparent paradox of an alpha2A-autor...

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Section: Subclassification Of α 2 -Autoreceptorssupporting

confidence: 80%

A re-investigation of questionable subclassifications of presynaptic α2-autoreceptors: rat vena cava, rat atria, human kidney and guinea-pig urethra

Trendelenburg

Sutej

Wahl

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Chiu et al (1995) recently suggested that the LC autoreceptors are α 2A on the basis of the prazosin and yohimbine data also included here in Table 1A, and of an inhibitory effect of oxymetazoline. They do not discuss the pharmacological α 2A /α 2D heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…They do not discuss the pharmacological α 2A /α 2D heterogeneity. What Chiu et al (1995) demonstrate is, in our terminology, an α 2A/D character of the autoreceptors. Our study confirms this with three main sets of data and identifies in addition the receptors as the α 2D variant.…”

Section: Discussionmentioning

confidence: 99%

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Subtype determination of soma-dendritic α2-autoreceptors in slices of rat locus coeruleus

Nörenberg

Schöffel

Szabó

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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The aim of the study was to subclassify the soma-dendritic alpha2-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average rate of 1 Hz. The selective alpha2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential discharge with IC50 values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the right by phentolamine (0.15 microM) and rauwolscine (0.15 microM) but not by prazosin (1 microM). Apparent Kd values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent Kd values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 microM) suppressed the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored firing with EC50 values of 120 and 250 nM, respectively. Prazosin (1 microM) again was ineffective. All three antagonist affinity estimates - against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the presence of oxaprotiline) - yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even at a concentration of 1 microM. These findings identify the soma-dendritic alpha2-autoreceptors of the LC as the rat variant of the alpha2A/D-adrenoceptor, i.e. alpha2D. Not only presynaptic but also soma-dendritic alpha2-autoreceptors may at least predominantly be alpha2A/D throughout the nervous system.

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“…O mecanismo de ação básico dos agonistas dos receptores adrenérgicos do tipo α-2 é caracterizado por diminuir a liberação de noradrenalina (NA) central e perifericamente, diminuindo a concentração de catecolaminas circulantes (em até 90%) e atenuando a excitação do sistema nervoso central (SNC), especialmente na região conhecida por locus coeruleus (CHIU et al, 1995). Nesse local, os efeitos são controlados por receptores α-2 A (CALLADO; STAMFORD, 1999 A dexmedetomidina é um D-isômero com alta especificidade por receptores α-2 (10 vezes mais, quando comparada à xilazina), que somada à levomedetomidina, o L-isômero, produz a mistura racêmica conhecida por medetomidina, descrita há 16 anos (SAVOLA et al, 1986apud CULLEN, 1996.…”

Section: Farmacologiaunclassified

Dexmedetomidina, uma nova opção na anestesiologia veterinária

Baldo

Nunes

2003

Sem. Ci. Agr.

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ResumoCom este trabalho, os autores procuram fornecer informações sobre o uso da dexmedetomidina, um novo agonista dos receptores adrenérgicos do tipo α-2, na prática anestésica. São tecidas considerações relativas ao emprego e a farmacologia desse novo agente, suas vantagens e restrições de uso, bem como a avaliação quanto à sua eficiência e segurança quando utilizado em associação a outros agentes anestésicos. Complementarmente, procurou-se atualizar com literatura recente os conhecimentos dos profissionais que militam na área de Anestesiologia Veterinária. Palavras-chave: Dexmedetomidine, anestesiologia veterinária. AbstractThe aim of this work was to provide information about the use of dexmedetomidine, a new α-2 agonist, in anesthetic practice. They comment about the pharmacology, its advantages and disadvantages, its efficiency and safety when associated with others anesthetic agents. Complementary, it was aimed to update the professionals that work with Veterinary Anesthesiology, through new papers and reports.

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Action of dexmedetomidine on rat locus coeruleus neurones: intracellular recording in vitro

Cited by 76 publications

References 35 publications

A re-investigation of questionable subclassifications of presynaptic α2-autoreceptors: rat vena cava, rat atria, human kidney and guinea-pig urethra

A re-investigation of questionable subclassifications of presynaptic α2-autoreceptors: rat vena cava, rat atria, human kidney and guinea-pig urethra

Subtype determination of soma-dendritic α2-autoreceptors in slices of rat locus coeruleus

Dexmedetomidina, uma nova opção na anestesiologia veterinária

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