Pharmacological effects of (+)-nantenine, an alkaloid isolated from Platycapnos spicata, in several rat isolated tissues.
In this work, the potential activity of (+)-nantenine (a natural aporphin alkaloid) in several rat isolated tissues was studied. In rat isolated intact aorta, (+)-nantenine (0.05 - 0.5 microM) competitively antagonized with almost equal effectiveness the contractions produced by phenylephrine (PE) and 5-hydroxytryptamine (5-HT) in normal Krebs solution. However, at higher concentrations (2 microM), the alkaloid also reduced the maximal effect induced by these two agonists. In depolarizing Ca2+-free high KCl 50 mM solution, (+)-nantenine (1.5 - 6 microM) inhibited, in a non-competitive way, the increase in tension evoked by Ca2+ with depression of the maximum response. On the other hand, (+)-nantenine (3 - 30 microM) did not affect the contractile effect caused by okadaic acid (OA, 1 microM) while, however, this alkaloid totally relaxed, in a concentration-dependent fashion, the contractions produced by phorbol 12-myristate 13-acetate (PMA, 1 microM) in endothelium-containing rat aortic rings. (+)-Nantenine (1 - 30 microM) reversed and competitively antagonized the inhibitory action induced by B-HT 920 in electrically-stimulated rat vas deferens. In isolated rat atria, (+)-nantenine (3 - 10 microM) diminished the contraction frequency. (+)-Nantenine (3 microM) significantly reduced the depolarization (voltage)-activated transient (T-type) and sustained (long-lasting, L-type) barium inward currents [ IBa(T) and IBa(L) ] recorded in whole cell-clamped rat aortic myocytes. These results indicate that the pharmacological effects of (+)-nantenine observed at concentrations lower than 1 microM can be attributed to alpha 1 -adrenergic and 5-HT 2A receptor blocking properties whereas at higher concentrations (> 1 microM) the pharmacological activity of this natural compound may be also due to a decrease of Ca2+ influx through transmembrane calcium channels (calcium antagonist activity), to an inhibition of PKC actions and/or to an alpha 2 -adrenoceptor blockade.
Orallo
Francisco
F
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain. fforallo@usc.es
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001060:Aporphines / Q000008:administration & dosage / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D028101:Papaveraceae; D010276:Parasympatholytics / Q000008:administration & dosage / Q000494:pharmacology*; D010656:Phenylephrine; D008517:Phytotherapy; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin; D014649:Vas Deferens / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000470:Alkaloids; D001060:Aporphines; D015220:Calcium Channels; D010276:Parasympatholytics; D014665:Vasodilator Agents; D010656:Phenylephrine; D012701:Serotonin; D011189:Potassium Chloride; C041615:nantenine