[3H]Noradrenaline-releasing action of vinpocetine in the isolated main pulmonary artery of the rabbit

Abstract

Abstract Vinpocetine (10−6 − 3 × 10−5 M) increased both the resting and the nerve stimulation-evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3 × 10−5 M; corticosterone, 5 × 10−5 M), and inhibited the nerve stimulation-evoked postsynaptic response. The resting transmitter releasing action of vinpocetine increased in the absence of cocaine. Exogenously applied (−)noradrenaline [(−)NA] (10−6 M) or clonidine (10−6 M) inhibited the vinpocetine (3 × 10−5 M)-potentiated [3H]NA release and contracted the circular muscle. The clonidine-induced contraction was abolished by 10−7 M prazosin. The inhibitory action of (−)-NA on vinpocetine-potentiated [3H]NA release was partly antagonized by 3 × 10−7 M yohimbine, a preferential α2-adrenoceptor blocker. In Ca-free Krebs solution containing 1 mM EGTA the neurotransmitter releasing action of vinpocetine was abolished, however, its stimulating action on the resting [3H]NA outflow was not changed. In Na-pump-inhibited arteries (K-free solution), where both the resting and the nerve stimulation-evoked release of neurotransmitter had already been increased, vinpocetine further enhanced the nerve stimulation-evoked release of [3H]NA. It is concluded that vinpocetine may have α2- and α1-adrenoceptor blocking action, as well as a tyramine-like effect. The presynaptic neurotransmitter releasing action of vinpocetine is presumably the consequence of its inhibitory action on the Ca-pump which is suggested by the finding that in K-free solution vinpocetine was able to enhance further the release of neurotransmitter.