α2A Adrenoceptors and non-adrenergic idazoxan binding sites in calf brain and retina are distinct from those in human brain

https://doi.org/10.1016/0197-0186(93)90046-8Get rights and content

Abstract

α2 Adrenoceptors in membrane preparations of human and calf frontal cortex and of calf retina can be labelled by the antagonists [3H]idazoxan, [3H]rauwolscine and [3H]RX 821002. Present and previous data indicate that [3H]idazoxan possesses the highest affinity for the α2 adrenoceptors in the calf tissues, whereas [3H]rauwolscine displays the highest affinity for those in the human frontal cortex. Competition binding experiments with adrenergic and serotonergic drugs further support the notion that the α2 adrenoceptors in calf frontal cortex and retina are similar, but distinct from the receptors in human frontal cortex. The α2 adrenoceptors in the three investigated tissues display low affinity for the antagonist prazosin, which suggests that they all belong to the α2A subclass. The competition binding curves of the α2A adrenoceptor subtype-selective agonist oxymetazoline are shallow, but undergo a rightward shift and steepening in the presence of GTP. The shallow curves can therefore be attributed to the coupling of the α2 adrenoceptors to G proteins. The different binding characteristics of the α2A adrenoceptors from the investigated human and bovine tissues are likely to reflect species-related differences in protein structure.

[3H]Idazoxan binds also to non-adrenergic sites in membrane preparations from the three tissues. However, the affinity of [3H]idazoxan for these sites in calf cortex and retina is appreciably lower than for those in human cortex. The species-related differences of the non-adrenergic idazoxan binding sites may be due to differences in protein structure or even to differences in gene-product.

References (41)

  • K.E.J. Dickinson et al.

    Heterogeneity of mammalian α2-adrenoceptors delineated by [3H]yohimbine binding

    Eur. J. Pharmac.

    (1986)
  • S.L. Jones et al.

    Characterisation of coeruleospinal inhibition of the nociceptive tail-flick reflex in the rat

    Brain Res.

    (1986)
  • D. Langin et al.

    Discrimination between α2-adrenoceptors and [3H]idazoxan-labelled non-adrenergic sites in rabbit white fat cells

    Eur. J. Pharmac.

    (1990)
  • P.J. Munson et al.

    LIGAND: a versatile computerised approach for characterisation of ligand binding systems

    Analyt. Biochem.

    (1980)
  • A.C. Petrash et al.

    Alpha2 adrenergic receptor subtypes indicated by [3H]yohimbine binding in human brain

    Life Sci.

    (1986)
  • F. Tesson et al.

    Subcellular distribution of imidazoline-guanidinium-receptive sites in human and rabbit liver

    J. biol. Chem.

    (1991)
  • P.B.M.W.M. Timmermans et al.

    Characterization of alpha-adrenoceptors participating in the central hypotensive and sedative effects of clonidine using yohimbine, rauwolscine and corynanthine

    Eur. J. Pharmac.

    (1981)
  • S. Uhlén et al.

    Delineation of rat kidney α2A- and α2B-adrenoceptors with [3H]RX821002 radioligand binding: computer modelling reveals that guanfacine is an α2A-selective compound

    Eur. J. Pharmac.

    (1991)
  • G. Vauquelin et al.

    Identification of α2 adrenergic receptors in human frontal cortex membranes by binding of [3H]RX821002, the 2-methoxy analog of [3H]idazoxan

    Neurochem. Int.

    (1990)
  • J.E.S. Wikberg et al.

    Medetomidine stereoisomers delineate two closely related subtypes of idazoxan (imidazoline) I-receptors in the guinea pig

    Eur. J. Pharmac.

    (1991)
  • Cited by (0)

    View full text