Human brain imidazoline receptors: further characterization with [3H]clonidine.
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.
Bricca
G
G
Laboratoire de Pharmacologie Cardiovasculaire et Rénale, CNRS URA 589, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Greney
H
H
Zhang
J
J
Dontenwill
M
M
Stutzmann
J
J
Belcourt
A
A
Bousquet
P
P
D001667:Binding, Competitive; D001933:Brain Stem / Q000378:metabolism*; D003000:Clonidine / Q000031:analogs & derivatives / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology*; D006801:Humans; D054755:Imidazoline Receptors; D066298:In Vitro Techniques; D009278:Naphazoline / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism* / Q000502:physiology
D054755:Imidazoline Receptors; D011942:Receptors, Adrenergic, alpha; D011955:Receptors, Drug; D006165:Guanylyl Imidodiphosphate; D009278:Naphazoline; D003000:Clonidine