Adrenaline hypothesis: effect of formoterol on noradrenaline release.
1 Originally, the so-called 'adrenaline hypothesis' related the release of noradrenaline (NA) to stimulation of presynaptic beta2-receptors in nerve endings; now it confers a possible role to adrenaline taken up then released by nerves endings. It represents a potentially useful therapeutic pathway. The present study aims to investigate the effects of formoterol, a highly selective beta2-adrenoceptor agonist. 2 It was carried out in freely moving rats, the isotope dilution technique being used to measure the NA spill over rate (NA-SOR) and metabolic clearance rate (MCR). 3 A series of three results are reported. (a) When compared with adrenaline on equimolar basis, formoterol (2.3 micro kg-1 min-1) increased NA-SOR while mean arterial blood pressure was decreased and heart rate increased. Thus, it was difficult to separate a direct presynaptic effect from indirect baroreflex-dependent activation of the sympathetic system. (b) When formoterol was infused at 1 ng kg-1 min-1, a dose empirically defined to induce no haemodynamic effect, NA-SOR was significantly increased, while NA-MCR remained unchanged. (c) The NA-SOR response to formoterol was not amplified by the presynaptic alpha2-adrenoceptor blocker, yohimbine, in contrast to the NA-SOR response to adrenaline. 4 In conclusion, formoterol, a beta2-adrenoceptor agonist, is shown to increase the release and plasma concentration of NA while its clearance was not changed.
Maignan
E
E
Catecholamines Biology Research Laboratory, INSERM - Broussais Faculty of Medicine, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Advenier
C
C
Safar
M
M
Cuche
J L
JL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D018343:Receptors, Adrenergic, beta-2; D015016:Yohimbine; D000068759:Formoterol Fumarate; D009638:Norepinephrine; D004837:Epinephrine