Effect of a 7‐day treatment with idazoxan and its 2‐methoxy derivative RX 821001 on α<sub>2</sub>‐adrenoceptors and non‐adrenoceptor idazoxan binding sites in rabbits

Portillo, Marı́a P.; Reverte, M.; Langin, Dominique; Senard, Jean‐Michel; Tran, Marie-Antoinette; Berlan, Michel; Montastruc, Jean‐Louis

doi:10.1111/j.1476-5381.1991.tb12406.x

Cited by 16 publications

(4 citation statements)

References 32 publications

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“…Although the present experiments were not designed to investigate cellular mechanisms, one could hypothesize (as suggested by Costentin et al, 1975;) that tolerance to repeated injections of apomorphine involves D2 dopamine receptor desensitization. Our work also suggests a different time course of desensitization of D2 dopamine receptors involved in these mechanisms since tolerance to cardiovascular and emetic effects of apomorphine disappeared after 2 h and persisted for hypothermic effects for at least 2 h. Thus, as previously reported for 12- (Estan et al, 1990;Portillo et al, 1991) and 13-- (Chaudry & Granneman, 1994) adrenoceptors, the present study suggests a tissue-specific regulation of D2 dopamine receptors to repeated injection of apomorphine. Further studies are needed to investigate the mechanism of this tissue-specific regulation which could involve different D2 dopamine receptor subtypes or different receptor-coupling mechanisms (Andersen et al, 1990;Caccavelli et al, 1992).…”

Section: Discussionsupporting

confidence: 63%

A study of tolerance to apomorphine

Montastruc

Llau

Senard

et al. 1996

British J Pharmacology

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1 The present study was designed to investigate tolerance to several pharmacological effects of apomorphine. 2 Changes in blood pressure, heart rate, plasma noradrenaline levels, rectal temperature, respiratory rate and retching plus vomiting were compared after administration of apomorphine (200 jig kg-', i.v. as a bolus) or saline at different time intervals (30, 120 and 720 min) in four groups of chloraloseanaesthetized dogs. 3 The first administration of apomorphine induced a significant decrease in blood pressure and rectal temperature, a marked rise in heart rate with no change in noradrenaline plasma levels or respiratory rate. Emesis occurred in 71% of the animals. 4 A second administration of apomorphine 30 min later failed to modify blood pressure or heart rate. In contrast, the magnitude of apomorphine-induced changes in blood pressure and heart rate was similar to that observed after the first administration when apomorphine was given 120 or 720 min later. 5 The apomorphine-induced decrease in rectal temperature evoked by a second dose of apomorphine was less marked when given 30 and 120 min after the first dose and unchanged when given 720 min later. 6 The number of animals exhibiting retching and vomiting was lower when apomorphine was reinjected after 30 min than when the time between two successive injections of apomorphine was 120 or 720 min. 7 These results show that tolerance to apomorphine involves its cardiovascular, hypothermic and emetic effects. The time course of tolerance to repeated injections of apomorphine is longer for its hypothermic than for its hypotensive or emetic effects. This suggests a tissue-specific regulation of D2 dopamine receptors to repeated injections of apomorphine.

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Section: Discussionsupporting

confidence: 63%

A study of tolerance to apomorphine

Montastruc

Llau

Senard

et al. 1996

British J Pharmacology

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“…When comparing circulating levels of insulin after a glucose challenge in animals pretreated with any of the three drugs, idazoxan was able to induce the maximal response. The dual nature of this ligand should be borne in mind: its ability to block: 1) pre and post-synaptic  2 adrenoceptors and thus increase plasma catecholamine levels [50], with a subsequent -adrenoceptor mediated effect; and 2) K ATP channels as an I-ligand (like BU 224). Combined mechanisms would be responsible for such an effect.…”

Section: Discussionmentioning

confidence: 99%

Comparative effects of idazoxan, efaroxan, and BU 224 on insulin secretion in the rabbit: Not only interaction with pancreatic imidazoline I2 binding sites

Garcı́a-Barrado¹,

Pastor²,

Iglesias-Osma³

et al. 2010

Health

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The nature of the binding site(s) involved in the insulin secretory activity of imidazoline compo- unds remains unclear. An imidazoline I2 binding site (I2BS) has been neglected since the classic I2 ligand, idazoxan, does not release insulin. Using the rabbit as an appropriate model for the study of this type of binding sites, we have tried to re-evaluate the effects of idazoxan, the selective I2 compound BU 224, and efaroxan on insulin secretion. Mimicking efaroxan, idazoxan and BU 224 potentiated insulin release from perifused islets in the presence of 8 mM glucose. In static incubation, insulin secretion induced by idazoxan and BU 224 exhibited both dose and glucose dependencies. ATP-sensitive K+ (KATP) channel blockade, though at a different site from the SUR1 receptor, with subsequent Ca2+ entry, mediates the insulin releasing effect of the three ligands. However, additional MAO independent intracellular steps in stimulus- secretion coupling linked to PKA and PKC activation are only involved in the effect of BU 224. Therefore, both an I2 related binding site at the channel level shared by the three ligands and a putative I3-intracellularly located binding site stimulated by BU 224 would be mediating insulin release by these compounds. In vivo experiments reassess the abilities of idazoxan and BU 224 to enhance glucose-induced insulin secretion and to elicit a modest blood glucose lowering response

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“…When 0~a adrenoceptor blockers, agents that block the negative feedback of norepinephrine release (Vizi et al 1986;Harsing and Vizi 1991;Portillo et al 1991;Poncet et al 1992), were used to modulate the activation of the catecholaminergic system, contrasting results were obtained in mice and rats. In mice 0~2 adrenoceptor antagonists reduce aggressiveness in a variety of conditions (Kemble et al 1991;Matsumoto et al 1991;Rawleigh and Kemble 1992;Cai et al 1993).…”

Section: Introductionmentioning

confidence: 92%

The effect of α2 adrenoceptor blockers on aggressive behavior in mice: implications for the actions of adrenoceptor agents

1996

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The effects of three alpha 2 adrenoceptor blockers (idazoxan, yohimbine and CH-38083) on isolation-induced aggressive behavior was studied in male mice. The three drugs produced different behavioral profiles. Idazoxan reduced aggressiveness dose-dependently by decreasing the duration of offensive/aggressive interactions and increasing the duration of defensive behaviors. The other two drugs produced only parts of the dual action of idazoxan: yohimbine affected mainly defensive behaviors, while CH-38083 affected only the time spent with fighting. Saline injections per se also influenced behavior and, in contrast to alpha 2 adrenoceptor blockers, induced an increase in aggressiveness. These results are different from those previously obtained in rats, which show bell-shaped dose-response curves in response to alpha 2 adrenoceptor blockers (small doses increased, while large doses decreased aggression). It is postulated that the strong behavioral reaction of mice to the injection per se may mask the aggression-heightening effects of small doses of alpha 2 adrenoceptor blockers in this species. A theory is also presented regarding the complexity of adrenoceptor interactions when both pre-, and postsynaptic alpha 2 adrenoceptors are blocked.

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Effect of a 7‐day treatment with idazoxan and its 2‐methoxy derivative RX 821001 on α₂‐adrenoceptors and non‐adrenoceptor idazoxan binding sites in rabbits

Abstract: 1The present study investigates the influence of a 7-day treatment with 2 mg kg- ',

Cited by 16 publications

References 32 publications

A study of tolerance to apomorphine

A study of tolerance to apomorphine

Comparative effects of idazoxan, efaroxan, and BU 224 on insulin secretion in the rabbit: Not only interaction with pancreatic imidazoline I2 binding sites

The effect of α2 adrenoceptor blockers on aggressive behavior in mice: implications for the actions of adrenoceptor agents

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Effect of a 7‐day treatment with idazoxan and its 2‐methoxy derivative RX 821001 on α2‐adrenoceptors and non‐adrenoceptor idazoxan binding sites in rabbits

Abstract: 1The present study investigates the influence of a 7-day treatment with 2 mg kg- ',

Cited by 16 publications

References 32 publications

A study of tolerance to apomorphine

A study of tolerance to apomorphine

Comparative effects of idazoxan, efaroxan, and BU 224 on insulin secretion in the rabbit: Not only interaction with pancreatic imidazoline I2 binding sites

The effect of α2 adrenoceptor blockers on aggressive behavior in mice: implications for the actions of adrenoceptor agents

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Effect of a 7‐day treatment with idazoxan and its 2‐methoxy derivative RX 821001 on α₂‐adrenoceptors and non‐adrenoceptor idazoxan binding sites in rabbits