[3H]‐MK 912 binding delineates two α2‐adrenoceptor subtypes in rat CNS one of which is identical with the cloned pA2d α2‐adrenoceptor

Uhlén, Staffan; Xia, Yifeng; Chhajlani, Vijay; Felder, Christian C.; Wikberg, Jarl E. S.

doi:10.1111/j.1476-5381.1992.tb14446.x

Cited by 87 publications

(33 citation statements)

References 31 publications

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“…prefrontal cortex, striatum) suggests their involvement in mediating the effects of ␣ 2 -adenoceptors agonists on working memory [1,36]. In our experimental conditions, the ␣ 2B,C -adrenoceptor antagonists ARC-239 and prazosin [47] were unable to prevent the amnesia induced by clonidine and guanabenz indicating that the adreneceptor subtype responsible for the induction of memory impairment by the ␣ 2 -agonists in a passive avoidance paradigm does not belong to the ␣ 2B and ␣ 2C subtypes. Similar results have been obtained investigating the ␣ 2 -adrenoceptor subtype involved in the memory enhancing properties of ␣ 2 -adrenoceptor agonists.…”

Section: Discussionmentioning

confidence: 80%

Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype

Galeotti¹,

Bartolini²,

Ghelardini³

2004

Behavioural Brain Research

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The activation of ␣ 2 -adrenoceptors has been reported to impair memory functions in both rats and humans. The ␣ 2 -adrenoceptor subtype responsible for this detrimental effect is still unknown. The effect of the ␣ 2 -agonists clonidine and guanabenz on memory processes, in dependence to the time of administration, was evaluated in the mouse passive avoidance test. Clonidine (0.02-0.2 mg kg −1 i.p.) and guanabenz (0.1-0.3 mg kg −1 i.p.) induced amnesia in a dose-dependent manner. From time-course experiments emerged that the impairment of memory function was detectable only when clonidine and guanabenz were administered 60 min before or immediately after the training test, respectively. This detrimental effect was prevented by pretreatment with the ␣ 2 -antagonist yohimbine (1-3 mg kg −1 i.p.) and by the ␣ 2A -antagonist BRL-44408 (0.3-1 mg kg −1 i.p.). By contrast, the ␣ 2B,C antagonists ARC-239 (10 mg kg −1 i.p.) and prazosin (1 mg kg −1 i.p.) did not revert the amnesia induced by both clonidine and guanabenz. At the highest effective doses, clonidine and guanabenz were devoid of behavioral side-effects as well as maintained unaltered the motor coordination, as revealed by the rota-rod test. Furthermore, none of the compounds used modified the spontaneous motility as indicated by the Animex apparatus. These results indicate that clonidine and guanabenz impaired memory processes in a mouse passive avoidance paradigm through the selective activation of the ␣ 2A -adrenoceptor subtype.

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Section: Discussionmentioning

confidence: 80%

Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype

Galeotti¹,

Bartolini²,

Ghelardini³

2004

Behavioural Brain Research

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“…There are no pharmacological data concerning the a2c-adrenoceptor subtype but methoxy-idazoxan, atipamezole, prazosin and yohimbine have been shown to bind to this subtype. The experiments of Uhlen et al (1992) on a2A-adrenoceptor and OC2c-adrenoceptor subtypes indicate a slightly higher affinity of clonidine and methoxy-idazoxan for a2A-adrenoceptors, a higher affinity of BRL44408 for the a2A-adrenoceptor subtype and a higher affinity of yohimbine and prazosin for a2C-adrenoceptors. A higher affinity of clonidine for 062A-adrenoceptors than for a2B and a2c-adrenoceptors was described by Harrison et al (1991).…”

Section: Reversal Of the Central Action Of Clonidinementioning

confidence: 90%

“…A second point of the studies by Ernsberger et al, was the correlation between the hypotensive effects of the drugs in the rat and their binding affinity at a2-adrenoceptors and imidazoline sites in the bovine brain; later studies have illustrated that some of the drugs (e.g. oxymetazoline and clonidine) that decrease blood pressure very effectively in their studies have a good and specific affinity for a2A-adrenoceptors in the rat (Harrison et al, 1991;Uhlen et al, 1992) and that clonidine binds more effectively to a2-adrenoceptors than to imidazoline-binding sites (Langin et al, 1990;Wikberg et al, 1991). Binding data cannot easily be related to those obtained in functional studies, especially when species and tissue differences occur.…”

Section: Reversal Of the Central Action Of Clonidinementioning

confidence: 99%

A comparative study of the reversal by different α₂‐adrenoceptor antagonists of the central sympatho‐inhibitory effect of clonidine

Vayssettes-Courchay

Bouysset

Cordi

et al. 1996

British J Pharmacology

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1 The recovery of the clonidine-induced hypotension, bradycardia and sympatho-inhibition produced by several putative o2-adrenoceptor antagonists was investigated in pentobarbitone anaesthetized rats. The activity of four substances containing an imidazoline structure: idazoxan, methoxy-idazoxan, BRL44408 and atipamezole was compared with the effect of fluparoxan, yohimbine and L-657,743; in addition the effect of the ac-adrenoceptor antagonist, prazosin, was also studied. 2 Prazosin (0.03-1 mgkg-1, i.v.) failed to alter the sympatho-inhibitory and hypotensive effects of clonidine (10 ,ug kg'-, i.v.). L-657,743 (0.01-1 mg kg-', i.v.) induced a recovery of blood pressure, heart rate and renal sympathetic nerve activity. Yohimbine (0.03-3 mg kg-1, i.v.) completely reversed the sympatho-inhibitory effect of clonidine but did not alter its hypotensive effect. 3 The four imidazoline drugs: idazoxan (10-300 ,ug kg-1, i.v.), methoxy-idazoxan (1-100 mug kg 1, i.v.), BRL44408 (0.1-3 mg kg-1, i.v.) and atipamezole (0.03-1 mg kg-', i.v.) and fluparoxan (10-300 jg kg-1, i.v.) reversed the clonidine-induced hypotension but produced only a partial recovery of the renal sympathetic nerve activity and of the heart rate. After pretreatment with prazosin (0.1 mg kg-', i.v.), the recovery of the sympathetic nerve activity elicited by these compounds was significantly higher. In hexamethonium (10 mg kg-1, i.v.) pretreated rats, these five drugs induced dose-related hypertension which was reduced by pretreatment with prazosin (0.1 mg kg-1, i.v.). 4 Our results indicate that the putative CX2-adrenoceptor antagonists idazoxan, methoxy-idazoxan, BRL44408, atipamezole and fluparoxan also have a peripheral hypertensive effect which is mediated through activation of vascular a1-adrenoceptors; this property of the compounds may be partly responsible for the reversal of the hypotensive action of clonidine. Considering the structure and the affinities of the drugs tested, our data indirectly suggest that a2A-adrenoceptors may be implicated in the central sympatho-inhibitory effects of clonidine.

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“…Means + s.e.mean (vertical lines) of 4-17 experiments are shown. Bylund et al, 1988;1994;Cheung et al, 1982;Devedijan et al, 1994;Gleason & Hieble 1992;Laftipour et al, 1982;Link et al, 1992;MacKinnon et al, 1992;Renouard et al, 1994;Ruffolo et al, 1991;Simonneaux et al, 1991;Uhlen et al, 1992;1994;Weinshank et al, 1990. Cholinoceptor-mediated effects on 5-HT outflow…”

Section: Resultsmentioning

confidence: 99%

Adrenoceptor‐ and cholinoceptor‐mediated mechanisms in the regulation of 5‐hydroxytryptamine release from isolated tracheae of newborn rabbits

Freitag

Wessler

Racké

1996

British J Pharmacology

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1 Isolated tracheae of newborn rabbits were incubated in vitro and the outflow of 5-hydroxytryptamine (5-HT) was determined by h.p.l.c. with electrochemical detection. Evidence has previously been provided that this 5-HT outflow derives from neuroendocrine epithelial (NEE) cells of the airway mucosa. 4 5-HT outflow evoked by 10 IM phenylephrine was inhibited by 65% in the presence of 1 gM forskolin and abolished in the presence of 10 gM forskolin. 5 5-HT outflow evoked by 10 gM phenylephrine was inhibited by about 45 and 70% in the presence of 0.1 and 1 gM isoprenaline, respectively. The inhibitory effect of 1 gM isoprenaline was only marginally antagonized by 1 gM, but blocked by 10 gM propranolol.6 5-HT outflow was not affected by the muscarine receptor agonist oxotremorine (10 gM), but was enhanced by 175% by 100 gM nicotine. The effect of nicotine was blocked by 100 gM hexamethonium and prevented by 1 gM tetrodotoxin or 1 gM yohimbine. 7 In conclusion, 5-HT release from NEE cells of the rabbit trachea is stimulated via a-adrenoceptors most likely of the a2B-subtype localized directly at the NEE cells. Activation of ,B-adrenoceptors as well as direct activation of adenylyl cyclase by forskolin exert inhibitory effects on 5-HT release. Activation of nicotinic, but not of muscarinic receptors, also evokes the release of 5-HT. However, the effect of nicotine appears to be mediated indirectly via the release of noradrenaline.

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[³H]‐MK 912 binding delineates two α₂‐adrenoceptor subtypes in rat CNS one of which is identical with the cloned pA2d α₂‐adrenoceptor

Cited by 87 publications

References 31 publications

Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype

Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype

A comparative study of the reversal by different α₂‐adrenoceptor antagonists of the central sympatho‐inhibitory effect of clonidine

Adrenoceptor‐ and cholinoceptor‐mediated mechanisms in the regulation of 5‐hydroxytryptamine release from isolated tracheae of newborn rabbits

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[3H]‐MK 912 binding delineates two α2‐adrenoceptor subtypes in rat CNS one of which is identical with the cloned pA2d α2‐adrenoceptor

Cited by 87 publications

References 31 publications

Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype

Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype

A comparative study of the reversal by different α2‐adrenoceptor antagonists of the central sympatho‐inhibitory effect of clonidine

Adrenoceptor‐ and cholinoceptor‐mediated mechanisms in the regulation of 5‐hydroxytryptamine release from isolated tracheae of newborn rabbits

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[³H]‐MK 912 binding delineates two α₂‐adrenoceptor subtypes in rat CNS one of which is identical with the cloned pA2d α₂‐adrenoceptor

A comparative study of the reversal by different α₂‐adrenoceptor antagonists of the central sympatho‐inhibitory effect of clonidine