Presynaptic α2A/D-autoreceptors in the brain cortex of Cercopithecus aethiops

Trendelenburg, Anne‐Ulrike; Sutej, Igor; Starke, Klaus

doi:10.1007/pl00004952

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…Based mainly on observations on the rat and rabbit brain cortex we suggested 'that already the α 2A/D ancestor gene was expressed in noradrenergic neurones to yield presynaptic and, presumably, soma-dendritic α 2 -autoreceptors and that it is this branch of the α 2 -adrenoceptor tree to which the (main) mammalian α 2 -autoreceptors belong' . Many studies now support the predominant α 2A/D nature of presynaptic α 2 -autoreceptors (recent reports: Molderings and Göthert 1995;Smith et al 1995;Trendelenburg et al 1996aTrendelenburg et al , 1997Wahl et al 1996;Paiva et al 1997; for review see Starke et al 1995;Hieble et al 1997). However, there are apparent exceptions.…”

Section: Anne-ulrike Trendelenburg · Igor Sutej · Christian Andreas Wmentioning

confidence: 99%

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: Anne-ulrike Trendelenburg · Igor Sutej · Christian Andreas Wmentioning

confidence: 99%

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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“…According to Trendelenburg et al (1997b), p K d values against exogenous agonists are better indicators of the real affinity of antagonists than p EC 30% values, since any additional action of the antagonists other than α-adrenoceptor blockade might distort p EC 30% values without changing pK d values. In agreement with this view, in the major part of the studies aiming at subclassifying prejunctional α 2 -autoreceptors, pK d values were preferentially determined and the single pulse stimulation (Singer 1988) was used.…”

Section: Discussionmentioning

confidence: 99%

Prejunctional α2A-autoreceptors in the human gastric and ileocolic arteries

Guimarães

Figueiredo

Caramona

et al. 1998

Naunyn-Schmiedeberg's Arch Pharmacol

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This study was undertaken to determine the subtype of prejunctional alpha2-autoreceptors in human blood vessels. Segments of gastric and ileocolic arteries were incubated with [3H]noradrenaline and subsequently perifused with modified Krebs-Henseleit solution containing cocaine (12 microM). Five periods of electrical stimulation (S1-S5) were applied (1 Hz, 1 ms, 50 V for 1 min). Concentration-response curves for the facilitatory effect of eight alpha-adrenoceptor antagonists [rauwolscine, 2-[2-(2-methoxy-1,4-benzodioxanyl)] imidazoline (RX821002), yohimbine, phentolamine, idazoxan, 2-(2',6'-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxan (WB4101), spiroxatrine and prazosin] were determined. All antagonists enhanced the stimulation-evoked overflow of tritium, indicating the existence of alpha2-autoreceptors. The EC30% values of the antagonists (concentrations that increased the evoked overflow of tritium by 30%) were taken as a measure of affinity to the autoreceptors. Correlations between the pEC30% values obtained in the present study and the pKi values of the same antagonists at cloned human alpha2A-, alpha2B-, alpha2C-adrenoceptors expressed in Chinese hamster lung cells and at alpha2D-adrenoceptors in the rat submaxillary gland or the bovine pineal gland showed that the alpha2-autoreceptors in the human gastric and ileocolic arteries resemble most closely the alpha2A-subtype.

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“…The a 2A -subtype appears to be also involved-at least partly-in the vasoconstrictor effect of a 2 -adrenoceptor stimulants . Results of Trendelenburg et al (1997) indicated that presynaptic autoreceptors belong predominantly to a 2A/2D -adrenoceptor subtypes. Hein et al (1999) suggested that activation of a 2A -adrenergic receptor inhibits transmitter release at high stimulation frequencies, whereas the a 2C -subtype regulates release at lower levels and regulation at both high and low frequencies appears to be physiologically important.…”

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confidence: 98%

Pharmacological analysis of α2-adrenoceptor subtypes mediating analgesic, anti-inflammatory and gastroprotective actions

et al. 2009

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Our previous findings suggest that alpha(2)-adrenoceptor stimulants induce gastroprotective action, the effect is likely to be mediated by alpha(2B)-adrenoceptor subtype. Clonidine (0.094 micromol/kg p.o.) and rilmenidine (0.014 micromol/kg p.o.) in gastroprotective dose range, as well as ST-91 (2.2 micromol/kg p.o.), a clonidine analogue showing higher affinity to alpha(2B)-adrenoceptor subtype than to alpha(2A)-one, inhibited the carrageenan-induced hyperalgesia in Randall-Selitto test, the antinociceptive action was reversed by yohimbine (5 micromol/kg s.c.) and the alpha(2B)-adrenoceptor antagonist prazosin (0.24 micromol/kg i.p.). Similarly, clonidine and rilmenidine in the same dose range reduced the oedema formation induced by carrageenan, yohimbine and the alpha(2A)-adrenoceptor antagonist BRL-44408 (3 micromol/kg i.p.) inhibited the anti-inflammatory effect; however, prazosin failed to affect it. These results suggest that alpha(2B/C)-like adrenoceptor subtype may be involved in the antihyperalgesic action, but not in the antiphlogistic effect of alpha(2)-adrenoceptor stimulants. The later effect may be mediated by alpha(2A)-like adrenoceptor subtype.

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Presynaptic α2A/D-autoreceptors in the brain cortex of Cercopithecus aethiops

Cited by 6 publications

References 24 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

Prejunctional α2A-autoreceptors in the human gastric and ileocolic arteries

Pharmacological analysis of α2-adrenoceptor subtypes mediating analgesic, anti-inflammatory and gastroprotective actions

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