Br. J . Pharmac. (1975), 5 5 , 343-350 EVIDENCE F O R NORADRENALINE AND ADRENALINE AS SYMPATHETIC TRANSMITTERS I N T H E CHICKEN V.P. DeSANTIS, W . LANGSFELD, R . LINDMAR & K . LOFFELHOLZ Department o f Pharmacology, University o f Mainz, Obere Zahlbacher Strafle 67 , D-65 Mainz, Germany I T h e concentrations o f noradrenaline an d adrenaline i n various organs, arterial plasma a n d venous outflow from isolated hearts o f adult chickens have been determined. 2 T h e relative adrenaline concentrations (percentage o f t h e sum o f noradrenaline a n d adrenaline) i n t h e heart (33%), spleen (16%) and brain (26%) were higher than those found i n mammalian organs. Chemical sympathectomy b y pretreatment with 6-hydroxydopamine caused a decrease of t h e noradrenaline and adrenaline concentrations i n t h e heart t o 20 a n d 2 3% and i n t h e spleen t o 1 6 and 29%, respectively. 3 Stimulation o f t h e right sympathetic nerves, infusion o f tyramine o r infusion o f a modified Tyrode solution containing 1 0 8 m M K + and 44 m M N a + caused a n output o f both noradrenaline a n d adrenaline into t he perfusate o f isolated hearts. Th e relative adrenaline concentration i n t h e perfusate (20-28%) was n o t significantly different from t h e relative adrenaline concentration remaining i n these hearts (19-22%). I n t h e individual experiments, t h e noradrenaline: adrenaline ratios o f t h e stimulation perfusates were positively correlated with t h e ratios found i n t h e hearts. 4 Th e effects of noradrenaline a n d adrenaline on cardiac rate a n d tension development were studied i n spontaneously beating right atria a n d electrically driven left atria, respectively. I n addition, t h e arterial pressure rise in response t o noradrenaline or adrenaline wa s measured in chickens. It w a s found that t h e cardio-vascular potency o f noradrenaline, a s reflected by t h e increases in heart rate, cardiac tension development an arterial blood pressure, wa s n o t significantly different from that o f adrenaline. 5 I t i s concluded that, i n t h e chicken heart a n d spleen, both noradrenaline a n d adrenaline a c t a s sympathetic neurotransmitters. Introduction I t h a s been shown that both noradrenaline a n d adrenaline a re present i n th e brain and peripheral tissues of chicks a nd chickens (review b y Holzbauer & Sharman, 1972). Th e concentrations o f adrenaline found i n these tissues a re higher than in t h e corresponding tissues of mammals. Thus t h e question of whether noradrenaline o r adrenaline i s t h e sympathetic transmitter i n t h e chicken has been raised. Callingham & Cass (1966) speculating indirect evidence, suggested that adrenaline might fulfil this function and that noradrenaline acts only a s a precursor. However, Sturkie & Poorvin (1973) obtained direct evidence that noradrenaline i s a sympathetic transmitter b y showing that sympathetic nerve stimulation caused a release o f noradrenaline from t h e isolated heart o f t h e chicken. A s t h e authors did ot detect a release o f adrenaline following nerve stimulation, t h e fate and function o f adrenaline present i n sympathetically innervated organs remained obscure. Interestingly t h e same controversy exists amongst histologists using fluorescent histo- chemical techniques t o distinguish t h e roles o f noradrenaline a n d adrenaline i n adrenergic transmission (Bennett & Malmfors, 1970). Preliminary results of t h e present work were presented a t t h e meeting o f t h e Deutsche Pharmakologische Gesellschaft (Lindmar &