caa a22 4500 469079215 CHVBK 20180323132944.0 cr unu---uuuuu 170328e19920301xx s 000 0 eng 10.1007/BF00168694 doi (NATIONALLICENCE)springer-10.1007/BF00168694 SK&F 104078, a post-functionally selective α2-adrenoceptor antagonist in the human saphenous vein in vitro [Elektronische Daten] [Sonia Roberts, John Kelly, Michael Cawthorne, Matthew Sennitt] Summary: The present study investigated the effects of SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxy]-3methyl-1H,2,3,4,-tetrahydro-3-benzazapine) at pre- and post functional α2-adrenoceptors in the human isolated saphenous vein. Noradrenaline (0.001-100 μmol/l) produced concentration-dependent contractions of the human saphenous vein which were competitively antagonised by the α1-adrenoceptor antagonist prazosin (0.01-1.0 μmol/l) and the α2-adrenoceptor antagonist, rauwolscine (0.01-1.0 μmol/l), indicating the presence of both post functional α1- and α2-adrenoceptors in this preparation. The selective α2-adrenoceptor agonist, UK-14,304 (0.01-100 μmol/l) also produced concentration-dependent contractions of the human saphenous vein which were antagonised by both rauwolscine (0.1 μmol/l) and prazosin (0.1 μmol/l). In the presence of angiotensin II (0.05 μmol/l), which itself produced a transient contraction, rauwolscine (0.1 μmol/l) produced a rightward shift of the UK-14,304 concentration-response curve while prazosin (0.1 μmol/l) had no effect. SK&F 104078 (10.0 μmol/l) under these conditions also produced a rightward shift of the concentration-response curve to UK-14,304, but was at least 100-fold less potent than rauwolscine. At pre functional α2-adrenoceptors, exogenous noradrenaline (0.01 and 0.1 gmol/l) induced a concentration-dependent inhibition of stimulation-evoked [7-3H]-noradrenaline release from the human saphenous vein in vitro, which was antagonised by rauwolscine (0:1 μmol/l) and tolazoline (10.0 μmol/l) but not by SK&F 104078 (10.0 gmol/l).Rauwolscine (0.1 μmol/l) produced a small increase in stimulation-evoked [7-3H]-noradrenaline release while both tolazoline and SK&F 104078 failed to produce any enhancement in release in the absence of exogenous agonist atconcentrationsupto10 gmol/l.Insummary, noradrenaline and UK-14,304 contracted the human isolated saphenous vein by an action at both postfunctional α1- and α2-adrenoceptors. These data demonstrate that SK&F 104078 discriminates between post- and pre-junctional α2-adrenoceptors in the human isolated saphenous vein. Springer-Verlag, 1992 α2-Adrenoceptors nationallicence Post-functional nationallicence Prejunctional nationallicence Human nationallicence Saphenous vein nationallicence Roberts Sonia Beecham Pharmaceuticals Research Division, Yew Tree Bottom Road, Great Burgh, KT18 5XQ, Epsom, Surrey, UK aut Kelly John Beecham Pharmaceuticals Research Division, Yew Tree Bottom Road, Great Burgh, KT18 5XQ, Epsom, Surrey, UK aut Cawthorne Michael Beecham Pharmaceuticals Research Division, Yew Tree Bottom Road, Great Burgh, KT18 5XQ, Epsom, Surrey, UK aut Sennitt Matthew Beecham Pharmaceuticals Research Division, Yew Tree Bottom Road, Great Burgh, KT18 5XQ, Epsom, Surrey, UK aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 327-332 0028-1298 345:3<327 1992 345 210 https://doi.org/10.1007/BF00168694 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00168694 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Roberts Sonia Beecham Pharmaceuticals Research Division, Yew Tree Bottom Road, Great Burgh, KT18 5XQ, Epsom, Surrey, UK aut NATIONALLICENCE 700 1- Kelly John Beecham Pharmaceuticals Research Division, Yew Tree Bottom Road, Great Burgh, KT18 5XQ, Epsom, Surrey, UK aut NATIONALLICENCE 700 1- Cawthorne Michael Beecham Pharmaceuticals Research Division, Yew Tree Bottom Road, Great Burgh, KT18 5XQ, Epsom, Surrey, UK aut NATIONALLICENCE 700 1- Sennitt Matthew Beecham Pharmaceuticals Research Division, Yew Tree Bottom Road, Great Burgh, KT18 5XQ, Epsom, Surrey, UK aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 327-332 0028-1298 345:3<327 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer