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Pharmacological and molecular discrimination of brain I2-imidazoline receptor subtypes

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Abstract

I2-imidazoline receptors labelled with [3H]-idazoxan in the rabbit and rat brains displayed high and low affinity, respectively, for the guanidide amiloride; reinforcing the previous definition of I2A-imidazoline receptors expressed in the rabbit brain and Its-imidazoline receptors expressed in the rat brain. Other drugs tested displayed biphasic curves in competition experiments, indicating the existence of high and low affinity sites for both subtypes of I2-imidazoline receptors. Among the drugs studied, bromoxidine, moxonidine, (+)- and (-)-medetomidine and clorgyline were more potent on the high and/or low affinity sites of 12B- than on their corresponding of I2A-imida-zoline receptors (K iH ratios 20 to 65). No correlation was found for the potencies of the drugs tested at the low affinity sites of both I2-imidazoline receptor subtypes. Preincubation (30 min at 25°°C) with 10-6 M clorgyline reduced by 60% the B max of [3H]-idazoxan binding to I2 B-imidazoline receptors in the rat brain, but it did not affect the binding parameters of the radioligand saturation curves to I2A-imidazoline receptors in the rabbit brain. These results indicated that I2A- and I2B-imidazoline receptor subtypes differ in the pharmacological profiles of their high and low affinity sites and in the ability to irreversibly bind clorgyline. In rat cortical membranes western blot detection of immunoreactive imidazoline receptor proteins revealed a double band of ∼29/30 kDa and two less intense bands of ∼ 45 and ∼ 66 kDa. In rabbit cortical membranes the antibody used detected proteins of ∼ 30, ∼57 and ∼66 kDa. It is suggested that different imidazoline receptor proteins (∼45 vs ∼57 kDa) may account for the different pharmacological profiles of I2-imidazoline receptor subtypes.

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Authors and Affiliations

  1. Laboratory of Neuropharmacology, Department of Biology, University of the Balearic Islands, Cra. Valldemossa km 7.5, E-07071, Palma de Mallorca, Spain

    G. Olmos, R. Alemany & J. A. García-Sevilla

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  1. G. Olmos
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  2. R. Alemany
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  3. J. A. García-Sevilla
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Olmos, G., Alemany, R. & García-Sevilla, J.A. Pharmacological and molecular discrimination of brain I2-imidazoline receptor subtypes. Naunyn-Schmiedeberg's Arch Pharmacol 354, 709–716 (1996). https://doi.org/10.1007/BF00166896

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