Nitrooxy alkyl apovincaminate activates K+ currents in rat neocortical neurons.

The effects of nitrooxy alkyl apovincaminate VA-045 ((+)-eburunamenine-14-carboxylic acid(2-nitroxy-ethyl ester), VA) were investigated in acutely dissociated rat neocortical neurons by using a nystatin-perforated patch recording configuration. VA activated a steady-state outward current in a concentration-dependent manner, with an EC50 of 0.65 microM. The reversal potential for the current shifted 56.5 mV with tenfold changes in the extracellular K+ concentration, suggesting that the current was carried by K+. The VA-induced current was not suppressed by apamin (1 microM), charybdotoxin (1 microM), Cs+ (3 mM), Ba2+ (3 mM), 4-aminopyridine (10 mM) or glibenclamide (10 microM), whereas tetraethylammonium suppressed the current with an IC50 of 1.4 mM. These pharmacological properties of the VA-induced current were compatible with a slowly inactivating delayed rectifier current (I(K)). It was suggested that the current activated by VA was I(K). The VA-induced current was not affected by Ca2+ depletion or by staurosporine (0.1 microM), quinacrine (10 microM), wortmanin (1 microM) or genistein (1 microM). The intracellular perfusion of GDPbetaS (0.4 mM) also had no significant effect. Thus, VA may directly activate the K+ channels.

Trachealis responses induced by vincamine and vinpocetine; inhibition by indomethacin and Ca2+ dependence.

Vincamine in low concentrations induced a sustained contraction of the isolated guinea pig trachealis with long latency and slow onset and, in high concentrations, it induced relaxation which was potentiated in the precontracted trachealis. Vinpocetine had actions similar to those of vincamine on trachealis, however its relaxant effect was more pronounced. The vincamine-induced trachealis contraction was not changed by substance P desensitization, was reduced by tetrodotoxin, nifedipine and low Ca2+ high Mg2+ solution and increased in nominally Ca2+-free solution. The vincamine-induced relaxation of precontracted trachealis was increased by guanethidine and was not affected by propranolol, high Mg2+-low Ca2+ solution and tetrodotoxin. Vincamine- and vinpocetine-induced trachealis contraction as well as vinpocetine-induced relaxation at basal tension were abolished by indomethacin. Vincamine in a low concentration shifted to the left the concentration-effect curve for CaCl2 in the K+-depolarized trachealis, and shifted it to the right at a high concentration. Our results indicate that the contractile and relaxant actions of vincamine and vinpocetine on the guinea pig trachealis may be due to the generation of prostaglandins and to changes in the membrane Ca2+ fluxes and/or the intracellular Ca2+ distribution.

[Effect of L-eburnamonine on bronchial respiratory resistance in the anesthetized guinea pig. Comparison with vincamine]. / Action de la l'éburnamonine sur la résistance des bronches à l'insufflation chez le cobaye anesthésié. Comparaison avec la vincamine.

In anesthetized guinea pigs, i.v. injection of l-eburnamonine (l-E) induced a moderate constriction of bronchia. This bronchoconstriction was partially antagonized by atropine and brompheniramine and nearly completely inhibited by papaverine; methysergide was devoid of antagonistic activity. It was suggested that the contractive activity of l-E is complex and not specific. Similar results were obtained with vincamine (Vi) but vincamine's bronchoconstriction was not completely inhibited by papaverine. Furthermore, the bronchoconstrictor activity of Vi was more important and more durable than that of l-E.