Effect of the activation of alpha-adrenoreceptors on the synthesis and release of noradrenaline by peripheral adrenergic nerves in vivo.
The synthesis and release of noradrenaline (NA) in the heart and submaxillary glands were studied in the rat following s.c. injections of oxymetazoline (50 mug/kg) or noradrenaline (500 mug/kg). NA release was evaluated from the decline in tissular specific radioactivity after administration of 3H-NA and NA synthesis by the estimation of the amounts of 3H-NA synthesized from 3H-tyrosine (TY) or 3H-Dopa, 30 min after the injection. Oxymetazoline treatment delayed the release of NA, the NA biological half-lives rising from 12 up to 36 hours in the heart and from 5.9 up to 21 hours in sub-maxillary glands. This inhibitory effect on NA release was interpreted as the consequence of the stimulation of alpha-adrenoreceptors. Thirty minutes after its injection, oxymetazoline increased both NA endogenous levels and 3H-NA amounts formed from 3H-TY: 3H-NA specific activities were not significantly altered. NA treatment led to an acceleration of NA release in the heart (NA biological half-life decreasing from 12 to 2.2 hours) but not in sub-maxillary glands. After injection of 3H-TY, the amounts of 3H-NA found in the heart and sub-maxillary glands were strongly reduced. Similar results were observed in the heart using 3H-Dopa as a precursor. These data are interpreted as the consequence of the removal of the newly synthesized 3H-NA by exogenous NA. The results obtained with oxymetazoline point out a dissociation between the NA release which is reduced and the NA synthesis which is unaltered. This indicates that NA synthesis rate by sympathetic nerve terminals is not immediately regulated by its release intensity. These data do not support the end-product feedback inhibition hypothesis according to which tyrosine hydroxylase is regulated by the intraneuronal NA concentration.
D000320:Adrenergic Fibers / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D005246:Feedback; D006321:Heart / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism*; D010109:Oxymetazoline / Q000494:pharmacology; D010525:Peripheral Nerves / Q000378:metabolism*; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D011941:Receptors, Adrenergic; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D010109:Oxymetazoline; D009638:Norepinephrine