PREJUNCTIONAL ACTIONS OF PIRIBEDIL ON THE ISOLATED KIDNEY OF THE RABBIT: COMPARISON WITH APOMORPHINE

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Abstract
1 The effects of piribedil on contractile responses and noradrenaline release evoked by sympathetic nerve stimulation have been studied in the isolated kidney of the rabbit. These effects were compared to those of apomorphine.2 Electrical stimulation (2, 5 and 10 Hz) of sympathetic renal nerves produced frequency-dependent increases in perfusion pressure and noradrenaline release. Piribedil did not affect (0.1 mug/min) or diminished (1 and 10 mug/min) the stimulation-evoked increase in perfusion pressure, and increased noradrenaline release in a dose-dependent manner.3 Increases in renal perfusion pressure and noradrenaline release induced by electrical stimulation were decreased by apomorphine (0.1 and 1 mug/min). These inhibitory effects were more marked at low frequencies of stimulation and were prevented by haloperidol (0.2 mumol/1).4 Piribedil (0.1 and 1 mug/min) and apomorphine (0.1, 1 and 10 mug/min) did not affect the increases in renal perfusion pressure elicited by exogenously administered noradrenaline, but piribedil (10 mug/min) diminished them.5 In the presence of desipramine (0.5 mumol/l), piribedil (0.1, 1 and 10 mug/min) produced a dosedependent inhibition of the increases in renal perfusion pressure and noradrenaline release evoked by sympathetic nerve stimulation; the inhibitory effect of piribedil was more marked at low frequencies of stimulation and was prevented by haloperidol.6 Piribedil increased the resting release of noradrenaline from the rabbit kidney, in contrast to apomorphine, which was without effect.7 It is suggested that piribedil has a complex effect on sympathetic transmission. This drug exhibits an ;amphetamine-like' action, causing noradrenaline release from its postganglionic stores. This releasing effect masks an action on prejunctional inhibitory dopamine receptors. In addition, at high doses, piribedil exhibits a marked action on postjunctional sites, since it reduces the vasoconstrictor effect of exogenous noradrenaline.