ISSN:
1432-1912
Keywords:
Antihypertensive drug
;
Clonidine
;
Imidazoline receptor
;
Locus coeruleus
;
Noradrenergic neuron
;
Moxonidine
;
Rilmenidine
;
α2-adrenoceptor
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract α2-Adrenoceptor agonists inhibit the firing of locus coeruleus (LC) neurons. It was recently observed that the α2-adrenoceptor agonists clonidine, rilmenidine and cirazoline, when injected intravenously in anaestbetized rats pretreated with the irreversible α2-adrenoceptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), excite the LC. The effect was attributed to activation of 11 imidazoline receptors. The aim of the present experiments was to characterize the direct effect of α2-adrenoceptor and I1 imidazoline receptor agonists on LC neurons. Electrical activity of LC neurons was extracellularly recorded in midpontine slices prepared from the rat brain. Concentration-response curves were obtained for the α2-agonist noradrenaline and the mixed I1/α2-receptor agonists clonidine, rilmenidine and moxonidine in slices without treatment and in slices treated with 6-chloro-N-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SK&F86466) or EEDQ, α2-adrenoceptor antagonists with low affinity for I1 and I2 imidazoline receptors, respectively. All four agonists concentration-dependently reduced the firing rate of the neurons, with full inhibition at higher concentrations. SK&F86466 shifted the concentration-response curves of the agonists to the right; the calculated antagonist dissociation constants are compatible with an effect of the agonists on α2-adrenoceptors. EEDQ completely prevented the inhibition by the agonists. Neither in SK&F86466- nor in EEDQ-treated slices was an excitation by clonidine, rilmenidine and moxonidine observed. We conclude that the LC neurons do not possess functional I1 (and also no I2) imidazoline receptors. The effects of noradrenaline, clonidine, rilmenidine and moxonidine on the neurons can be fully explained with an interaction with inhibitory α2-adrenoceptors (probably of the α2D subtype). The excitation of the LC by imidazoline receptor agonists under in vivo conditions, hence, is not a direct effect on the neurons of the LC.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00169176
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