Tyramine-induced endogenous noradrenaline efflux from in situ cardiac sympathetic nerve ending in cats

With the use of dialysis technique, the effects of tyramine on in situ card iac sympathetic nerve endings were examined in anaesthetized cats. Dialysis probes were implanted in the left ventricular myocardium, and the concentr ation of dialysate noradrenaline (NA) served as an indicator of NA output a t the cardiac sympathetic nerve ending. Locally applied tyramine (600 mu M) increased dialysate NA levels from 17 +/- 1 (pg mL(-1)) to 3466 +/- 209 (p g mL(-1)). Pretreatment with reserpine (vesicle transport NA blocker 1 mu M ) did not affect tyramine-induced NA efflux. The tyramine-induced NA efflux was augmented by pretreatment with pargyline (1 mM) but suppressed by parg yline (10 mM). Pretreatment with alpha-methyl-tyrosine suppressed NA efflux evoked by tyramine. These pretreatments did not affect the time course of NA efflux but only altered peak height of NA efflux. The efflux of NA evoke d by tyramine was not associated with any reduction of dihydroxyphenylglyco l (DHPG). In contrast, in the pretreatment with reserpine, the efflux of NA was associated with a reduction of DHPG. This result suggests that NA grad uation between axoplasm and stored vesicle contributes to maintaining the a xoplasmic NA level during carrier-mediated outward NA transport. The tyrami ne-induced NA efflux provides a close reflection of the NA content at the n erve ending. With the use of dialysis, this experimental model is suitable for studying the mechanism of sympathomimetic amine-induced neurotransmitte r efflux.