Characterization of alpha 2-adrenoceptor binding properties of imidazoline-like drugs, azoloazepine derivatives and beta-phenethylamine-like drugs in human platelet membranes.
To characterize the agonist profile of alpha 2-adrenoceptor agonists (imidazoline-like drugs, azoloazepine derivatives, beta-phenethylamines-like drugs) on human platelets, the characteristics of alpha 2-adrenoceptors (KD, Bmax) have been evaluated and the affinity constants measured by displacement technique and computer-assisted analysis of the curves. Furthermore, since alpha 2-adrenoceptor agonists interact with the post-synaptic receptors in a calcium-operated channel, whether the effect of calcium-entry inhibitors (verapamil, nifedipine, diltiazem) is related to a competition with alpha 2-receptors has also been examined. By Scatchard analysis, it was calculated that in human platelets alpha 2-adrenoceptors have KD = 3.45 nM and Bmax = 247 fmol (mg protein)-1. As far as the potency is concerned, imidazoline-like drugs were the most potent agonists in human platelet alpha 2-adrenoceptors (guanabenz IC50 = 8.6 +/- 0.8 X 10(-8), B-HT 920 IC50 = 2.9 +/- 0.3 X 10(-7), (-)-adrenaline IC50 = 3.4 +/- 0.5 X 10(-7)). Among the calcium-entry inhibitors only verapamil antagonized [3H]rauwolscine binding: the effect was stereospecific, (-)-D 600 being more potent than (+)-D 600. Nifedipine and diltiazem did not affect alpha 2-receptor binding. It is concluded that human platelets alpha 2-receptors share the agonist potency profile of other tissues containing alpha 2-receptors (brain, pre-synaptic junction), and that among calcium-entry blockers only verapamil can antagonize alpha 2-agonists. Nifedipine and diltiazem do not appear to interact stereospecifically with alpha 2-adrenoceptors.
Vago
T
T
Meroni
R
R
Dagani
R
R
Baldi
G
G
Pagani
M
M
Bevilacqua
M
M
Norbiato
G
G
D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology; D000328:Adult; D001381:Azepines / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D015016:Yohimbine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D007093:Imidazoles; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine