Alpha 2C-adrenoceptors mediate contractile responses to noradrenaline in the human saphenous vein.
We have investigated the subtype of alpha 2-adrenoceptor mediating isometric contractions of human saphenous vein in comparison with alpha 2-adrenoceptor ligand binding sites. Postjunctional alpha 2-adrenoceptors in the human saphenous vein were investigated in terms of the ability of alpha 2-adrenoceptor antagonists to shift the contractile potency of noradrenaline. The following antagonists were employed (potencies, pKB, in human saphenous vein in parentheses): chlorpromazine (6.98 +/- 0.24), BDF 8933 (7.60 +/- 0.06), prazosin (6.62 +/- 0.15), ARC 239 (7.19 +/- 0.15), yohimbine (7.23 +/- 0.09), HV 723 (7.52 +/- 0.14), WB 4101 (7.90 +/- 0.06), SKF 104078 (6.55 +/- 0.08), BRL 44408 (5.72 +/- 0.21). Antagonist potency at postjunctional alpha 2-adrenoceptors was correlated with antagonist affinity at alpha 2-adrenoceptor ligand binding sites in membranes of human platelet (alpha 2A), rat kidney (alpha 2B) and Sf9 cells expressing human recombinant receptors (alpha 2C), labelled with [3H]yohimbine. The correlation with the postjunctional alpha 2-adrenoceptor mediating contraction of the human saphenous vein was best for the human recombinant alpha 2C-adrenoceptor ligand binding site (r = 0.92, n = 8, P < 0.001), as compared to correlations with the alpha 2B-adrenoceptor ligand binding site of rat kidney (r = 0.62, n = 8, n.s.) and with the alpha 2A-adrenoceptor ligand binding site of human platelet (r = 0.23, n = 8, n.s.). It is concluded that the functional postjunctional alpha 2-adrenoceptor mediating contractions of the human saphenous vein closely resembles the human recombinant alpha 2C-adrenoceptor ligand binding site.
Gavin
K T
KT
Department of Physiology, Royal College of Surgeons in Ireland, Dublin, Ireland.
Colgan
M P
MP
Moore
D
D
Shanik
G
G
Docherty
J R
JR
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D012501:Saphenous Vein / Q000187:drug effects*
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D009638:Norepinephrine