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Stimulation of locus coeruleus neurons by non-I1/I2-type imidazoline receptors: an in vivo and in vitro electrophysiological study.

Abstract：

:1. Imidazoline binding sites have been reported to be present in the locus coeruleus (LC). To investigate the role of these sites in the control of LC neuron activity, we studied the effect of imidazolines using in vivo and in vitro single-unit extracellular recording techniques. 2. In anaesthetized rats, local (27 pmoles) and systemic (1 mg kg(-1), i.v.) administrations of 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a selective I-imidazoline receptor ligand, increased the firing rate of LC cells (maximal increase: 22+/-5%, P<0.001 and 16+/-7%, P<0.001 respectively). Chronic pretreatment with the irreversible monoamine oxidase inhibitor clorgyline (3 mg kg(-1), i.p., every 12 h for 14 days) abolished this effect. 3. In rat midpontine brain slices containing the LC, bath application (1 mM) of the imidazolines 2-BFI, 2-(4,5-dihydroimidaz-2-yl)-quinoline (BU224), idazoxan, efaroxan, phentolamine and (2-2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline (RX821002) reversibly stimulated LC cells. The maximal effect was approximately 90% except for RX821002 and efaroxan which induced smaller maximal effects (approximately 58% and approximately 35% respectively). Simultaneous application of idazoxan and 2BFI did not lead to additive effects. 4. Bath application of the alpha2-adrenoceptor antagonists, yohimbine (1 - 10 microM) and N-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) (10 microM), failed to modify LC activity. The irreversible blockade of alpha2-adrenoceptors with EEDQ (10 microM) did not alter the effect of idazoxan or that of efaroxan. Previous application of clorgyline (10 microM) did not modify the excitatory effect of 2-BFI or efaroxan. 5. Changes in the pH of the bathing solution (6.84-7.84) did not influence the effect caused by idazoxan. Bath application of 2-BFI (1 mM) reversed the inhibition induced by diazoxide (300 microM), an ATP-sensitive K+ channel opener, whereas application of glibenclamide (3 microM), an ATP-sensitive K+ channel blocker, partially blocked the effect of 2-BFI. 6. This study shows that imidazoline compounds stimulate the firing rate of LC neurons. This effect is not mediated by alpha2-adrenoceptors nor by I1 or I2-imidazoline receptors but involves a different subtype of imidazoline receptor. Our results indicate that this receptor is located extracellularly and modulates ATP-sensitive K+ channels.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Ugedo L,Pineda J,Ruiz-Ortega JA,Martín-Ruiz R

doi

10.1038/sj.bjp.0702255

subject

Has Abstract

pub_date

1998-12-01 00:00:00

pages

1685-94

issue

eissn

0007-1188

issn

1476-5381

journal_volume

125

pub_type

杂志文章

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Stimulation of locus coeruleus neurons by non-I1/I2-type imidazoline receptors: an in vivo and in vitro electrophysiological study.