Do alpha 2-adrenoceptors and imidazoline binding sites coexist in the human term placenta? Evidence from direct binding studies.
Alpha2-Adrenergic receptors and non-adrenergic imidazoline binding sites (IBS) in human placental membranes were investigated by means of the radioligands [3H]-RX 821002 and [3H]-RX 781094 (idazoxan) respectively. Human term placentae (38-40 weeks) were obtained immediately after vaginal delivery. The specific binding of the alpha2-subtype-selective [3H]-RX 821002 confirms the presence of alpha2-adrenoceptors in the human placenta, while [3H]-idazoxan binds to non-adrenergic IBS. The sites were characterized by displacement analyses with various imidazoline and non-imidazoline drugs. The presence of an endogenous ligand for IBS has not yet been demonstrated. Clonidine displacing substance (CDS) was recently identified as agmatine; it recognizes both alpha2 and imidazoline receptors. This phenomenon was studied in crude placental membranes. The studies revealed that: (i) alpha2-adrenoceptors coexist with non-adrenergic IBS in human placental membranes; (ii) there is a strong probability that alpha2-adrenoceptors and IBS are pharmacologically distinct; and (iii) agmatine binds to placental alpha2 and imidazoline receptors with different affinities.
Bagaméry
K
K
Department of Obstetrics and Gynaecology, WHO Collaborating Centre for Research in Human Reproduction, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Kovács
L
L
Nyári
T
T
Falkay
G
G
D001667:Binding, Competitive / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism* / Q000494:pharmacology; D054755:Imidazoline Receptors; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects; D011869:Radioligand Assay; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry* / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*
D007093:Imidazoles; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C058525:2-methoxyidazoxan; C014282:cirazoline; D019329:Idazoxan