The physiological and pharmacological role of presynaptic alpha- and beta-adrenoceptors in man.
Two studies were performed each in six normal volunteers in order to find evidence of either a physiological or pharmacological role of presynaptic alpha- and presynaptic beta-adrenoceptors in man. In Study 1 subjects received a 60 min infusion of guanfacine 3 mg (alpha 2-adrenoceptor agonist) preceded by either idazoxan (alpha 2-adrenoceptor antagonist) or vehicle. Guanfacine reduced plasma noradrenaline concentration by approximately 30% and this fall was not antagonised by the alpha 2-receptor antagonist. The 30-fold increase in plasma growth hormone, measured as a marker of the central action of guanfacine, was almost completely blocked by idazoxan. A comparison of the drug concentrations of idazoxan and guanfacine, together with their relative affinities for alpha 2-adrenoceptors, suggested that the idazoxan could not block the peripheral actions of guanfacine and that these were responsible for the fall in plasma noradrenaline concentration. In Study 2 adrenaline 0.05 micrograms kg-1 min-1 was infused for 80 min preceded by either idazoxan or vehicle. After vehicle, adrenaline caused no change in plasma noradrenaline concentration whereas it rose approximately 25% after administration of idazoxan. This was probably due to unmasking of presynaptic beta-adrenoceptor stimulation by adrenaline when the opposing inhibitory autoreceptor was blocked.
Brown
M J
MJ
Struthers
A D
AD
Burrin
J M
JM
Di Silvio
L
L
Brown
D C
DC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D019329:Idazoxan; D007328:Insulin / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010648:Phenylacetates / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D004146:Dioxanes; D006146:Guanidines; D007328:Insulin; D010648:Phenylacetates; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D017981:Receptors, Neurotransmitter; D016316:Guanfacine; C026777:ICI 118551; D009638:Norepinephrine; D019329:Idazoxan