The effect of S-(+)-boldine on the α1-adrenoceptor of the guinea-pig aorta
| Autor: | Emmanuel Naline, Susana Chuliá, Charles Advenier, M. Pilar D'ocon, M. Antonia Noguera, Joelle Moreau, M. Dolores Ivorra |
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| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_specialty Aporphines Contraction (grammar) Phosphodiesterase Inhibitors Muscle Relaxation Guinea Pigs Aorta Thoracic In Vitro Techniques Phosphatidylinositols Muscle Smooth Vascular chemistry.chemical_compound Caffeine Papaverine Receptors Adrenergic alpha-1 Internal medicine medicine.artery medicine Prazosin Animals Boldine Thoracic aorta Adrenergic alpha-Antagonists Pharmacology Parasympatholytics Calcium Channel Blockers Trachea Endocrinology chemistry Competitive antagonist Adrenergic alpha-1 Receptor Antagonists Histamine Acetylcholine Research Article medicine.drug |
| Zdroj: | British Journal of Pharmacology. 119:1305-1312 |
| ISSN: | 0007-1188 |
| Popis: | 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 Ca2+, and on guinea-pig trachea contracted with acetylcholine or histamine. 2. S-(+)-boldine inhibited in a concentration-dependent manner the contractile response evoked by noradrenaline (10 microM) in guinea-pig aorta (IC50 = 1.4 +/- 0.2 microM) while the KCl depolarizing solution (60 mM)- or the Ca2+ (1 mM)-induced contractions were only partially affected by boldine up to 300 microM. In contrast, papaverine relaxed noradrenaline (NA), KCl or Ca2+ induced contractions showing similar IC50 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 alpha 1-adrenoceptor blocking agent in guinea-pig aorta as revealed by its competitive antagonism of noradrenaline-induced vasoconstriction (pA2 = 5.64 +/- 0.08), and its potency was compared with that of prazosin (pA2 = 8.56 +/- 0.24), a known potent alpha 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 microM). Papaverine inhibited partially this caffeine-induced contraction at the maximal dose used (100 microM). 5. Inositol phosphates formation induced by noradrenaline (10 microM) in guinea-pig thoracic aorta was inhibited by S-(+)-boldine (30 microM) but not by papaverine (10 microM). 6. Contractions of guinea-pig trachea caused by acetylcholine (100 microM) or histamine (10 microM) were not modified by S-(+)-boldine (0.1-100 microM). 7. These results provide evidence that S-(+)-boldine, an aporphine alkaloid, has interesting properties as an alpha 1-adrenoceptor blocker in vascular smooth muscle, and acts as a competitive antagonist of the alpha 1-adrenoceptor present in the guinea pig aorta. |
| Databáze: | OpenAIRE |
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