Co-released adrenaline markedly facilitates noradrenaline overflow through prejunctional β2-adrenoceptors during swimming exercise

Abstract

The effect of intravenously applied (−)-adrenaline, taken up by and released from sympathetic nerves, on swimming exercise-induced noradrenaline overflow in permanently cannulated adrenal demedullated rats was studied. Adrenaline (100 ng/min) was infused for 2 h, during which a plasma concentration of 500 pg/ml (approximately 2.5 nM) was reached. One hour later plasma adrenaline had returned to undetectable levels. During swimming, adrenaline was released into the plasma in concentrations up to 133 pg/ml and the noradrenaline concentration was markedly enhanced as well. The total catecholamine increase amounted to 178% of control (saline infusion) in the first 3 min of swimming and 165% for the whole 20 min. Cocaine (2.5 mg/kg plus 0.05 mg/kg/min), infused together with adrenaline and continued throughout the experiment, prevented the exercise-induced release of adrenaline and no increase in plasma noradrenaline concentration was observed. Yohimbine (0.25 mg/kg) strongly further enhanced the exercise-induced overflow of both noradrenaline and adrenaline. This further increase was completely blocked by the selective β 2-adrenoceptor antagonist ICI 118,551 ((±)-1-[(2,3-dihydro-7-methyl-1 H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol) (1.0 mg/kg). These results demonstrate that adrenaline can be taken up by sympathetic nerve endings through cocaine-sensitive uptake carriers and is released from these nerves during swimming exercise. Neuronally released adrenaline markedly enhances exercise-induced catecholamine overflow through activation of prejunctional β 2-adrenoceptors.