title: Co-released adrenaline markedly facilitates noradrenaline overflow through prejunctional beta 2-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 beta 2-adrenoceptor antagonist ICI 118,551 ((+/-)-1-[(2,3-dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methyleth yl) 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 beta 2-adrenoceptors.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, University of Groningen, Netherlands.
authors.forename: R P
authors.initials: RP
authors.lastname: Coppes
authors.forename: J
authors.initials: J
authors.lastname: Smit
authors.forename: L
authors.initials: L
authors.lastname: Benthem
authors.forename: J
authors.initials: J
authors.lastname: Van der Leest
authors.forename: J
authors.initials: J
authors.lastname: Zaagsma
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D004837:Epinephrine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*; D013550:Swimming / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D015016:Yohimbine; C026777:ICI 118551; D003042:Cocaine; D009638:Norepinephrine; D004837:Epinephrine