The effect of S ‐(+)‐boldine on the α 1 ‐adrenoceptor of the guinea‐pig aorta

1 The cardiovascular activity of S ‐(+)‐boldine, an aporphine alkaloid structurally related to papaverine, was determined. The work includes functional studies on guinea‐pig isolated aorta contracted with noradrenaline, caffeine, KCl or Ca 2+ , and on guinea‐pig trachea contracted with acetylcholine or histamine. 2 S ‐(+)‐boldine inhibited in a concentration‐dependent manner the contractile reponse evoked by noradrenaline (10 μ m ) in guinea‐pig aorta (IC 50 = 1.4 ± 0.2 μ m ) while the KCl depolarizing solution (60 mM)‐ or the Ca 2+ (1 mM)‐induced contractions were only partially affected by boldine up to 300 μ m . In contrast, papaverine relaxed noradrenaline (NA), KCl or Ca 2+ induced contractions showing similar IC 50 values in all cases. S ‐(+)‐boldine had a greater potency on the contraction elicited by NA whereas papaverine acted in a non‐selective manner. 3 S ‐(+)‐boldine was found to be an α 1 ‐adrenoceptor blocking agent in guinea‐pig aorta as revealed by its competitive antagonism of noradrenaline‐induced vasoconstriction (pA 2 = 5.64 ± 0.08), and its potency was compared with that of prazosin (pA 2 = 8.56 ± 0.24), a known potent α 1 ‐adrenoceptor antagonist. In contrast, papaverine caused rightward shifts of the NA concentration‐response curves with depression of maximal response indicating that it acts as a non‐competitive antagonist. 4 Contraction of guinea‐pig aorta induced by caffeine (60 mM) in a Ca 2+ ‐containing Krebs solution was not affected by a 60 min incubation period with different doses of S ‐(+)‐boldine (1–300 μ m ). Papaverine inhibited partially this caffeine‐induced contraction at the maximal dose used (100 μ m ). 5 Inositol phosphates formation induced by noradrenaline (10 μ m ) in guinea‐pig thoracic aorta was inhibited by S ‐(+)‐boldine (30 μ m but not by papaverine (10 μ m ). 6 Contractions of guinea‐pig trachea caused by acetylcholine (100 μ m ) or histamine (10 μ m ) were not modified by S ‐(+)‐boldine (0.1–100 μ m ). 7 These results provide evidence that S ‐(+)‐boldine, an aporphine alkaloid, has interesting properties as an α 1 ‐adrenoceptor blocker in vascular smooth muscle, and acts as a competitive antagonist of the α 1 ‐adrenoceptor present in the guinea pig aorta.