ALPHA(2C)-ADRENOCEPTORS MEDIATE CONTRACTILE RESPONSES TO NORADRENALINE IN THE HUMAN SAPHENOUS-VEIN

We have investigated the subtype of alpha(2)-adrenoceptor mediating is ometric contractions of human saphenous vein in comparison with alpha( 2)-adrenoceptor ligand binding sites. Postjunctional alpha(2)-adrenoce ptors in the human saphenous vein were investigated in terms of the ab ility of alpha(2)-adrenoceptor antagonists to shift the contractile po tency of noradrenaline. The following antagonists were employed (poten cies, 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), WE 4101 (7 .90+/-0.06), SKF 104078 (6.55+/-0.08), BRL 44408 (5.72+/-0.21). Antago nist potency at postjunctional alpha(2)-adrenoceptors was correlated w ith antagonist affinity at alpha(2)-adrenoceptor ligand binding sites in membranes of human platelet (alpha(2) A), rat kidney (alpha(2) B) a nd Sf9 cells expressing human recombinant receptors (alpha(2) C), labe lled with [H-3]yohimbine. The correlation with the postjunctional alph a(2)-adrenoceptor mediating contraction of the human saphenous vein wa s best for the human recombinant alpha(2 C)-adrenoceptor ligand bindin g site (r=0.92, n=8, P<0.001), as compared to correlations with the al pha(2) B-adrenoceptor ligand binding site of rat kidney (r=0.62, n=8, n.s.) and with the alpha(2) A-adrenoceptor ligand binding site of huma n platelet (r=0.23, n=8, n.s.). It is concluded that the functional po stjunctional alpha(2)-adrenoceptor mediating contractions of the human saphenous vein closely resembles the human recombinant alpha(2) C-adr enoceptor ligand binding site.