Human brain imidazoline receptors: further characterization with [3H]clonidine

• Published in: European journal of pharmacology Vol. 266; no. 1; p. 25
• Main Authors: Bricca, G, Greney, H, Zhang, J, Dontenwill, M, Stutzmann, J, Belcourt, A, Bousquet, P
• Format: Journal Article
• Language: English
• Published: Netherlands 01-01-1994
• Subjects: Binding, Competitive; Brain Stem - metabolism; Clonidine - analogs & derivatives; Clonidine - metabolism; Guanylyl Imidodiphosphate - pharmacology; Humans; Imidazoline Receptors; In Vitro Techniques; Naphazoline - pharmacology; Receptors, Adrenergic, alpha - metabolism; Receptors, Drug - metabolism; Receptors, Drug - physiology
• ISSN: 0014-2999
• DOI: 10.1016/0922-4106(94)90205-4

The aim of the present study was to further characterize [3H]clonidine binding in the ventrolateral medulla of the human brainstem, the region involved in the vasodepressor effect of imidazoline drugs of the clonidine type. Under basal conditions, [3H]clonidine can bind both to the imidazoline receptors and to the alpha-adrenoceptors. The latter represent only a small part of the total [3H]clonidine binding with a Bmax of 61 +/- 13 fmol/mg proteins and a KD of 4.9 +/- 2.2 nM. Most of the binding was associated with imidazoline receptors with a KD of 67 +/- 13 nM and a Bmax of 677 +/- 136 fmol/mg protein. alpha-Adrenoceptor binding of [3H]clonidine could be completely prevented when membranes were either treated during preparation with the aIkylating agent phenoxybenzamine or incubated in the presence of 30 microM (-)-noradrenaline or in the presence of the non-hydrolysable analogue of GTP, guanylyl imidodiphosphate (Gpp(NH)p). When the alpha-adrenoceptors binding was prevented, we demonstrated the insensitivity of [3H]clonidine binding to Gpp(NH)p and showed that the competition between clonidine and idazoxan for imidazoline receptors was insensitive to Gpp(NH)p suggesting that imidazoline receptors are not G protein coupled receptors. The specificity of [3H]cloniding binding to imidazoline receptors in the human ventrolateral medulla indicates that these receptors are different from imidazole receptors as defined with p-aminoclonidine in the bovine brainstem.