Angiotensin-(1-7) does not affect norepinephrine neuronal uptake or catabolism in rat hypothalamus and atria.
1. Since we previously reported that angiotensin-(1-7) [Ang-(1-7)] increases or inhibits norepinephrine (NE) release in rat atria or hypothalamus, respectively, the present work was undertaken to investigate the effect of the heptapeptide on NE neuronal uptake and metabolism in atria and hypothalamus isolated from rats. 2. Ang II (1-10 microM) caused a decrease in neuronal NE uptake in both atria and hypothalami isolated from rats. On the contrary, tissues incubated with [3H]NE in the presence of 0.1-10 microM Ang-(1-7) showed no modification in [3H]NE content with respect to the control group, suggesting that the heptapeptide did not modify [3H]NE neuronal uptake. 3. To study the effect of the heptapeptide on NE catabolism, monoamine-oxidase (MAO) and catechol-O-methyltransferase (COMT) activities were determined. Pretreatment of the tissue with Ang-(1-7) (0.1-1.0 microM) showed a tendency to diminish MAO activity in rat atria, while no significant changes were observed in hypothalamic MAO activity. Moreover, the heptapeptide (0.1-1.0 microM) did not affect central COMT activity with respect to the control group. 4. Present results allow us to conclude that Ang-(1-7) interacts with noradrenergic neurotransmission by increasing or inhibiting NE release at the peripheral and central levels, respectively, without affecting either the neurotransmitter neuronal uptake or catabolism.
Gironacci
M M
MM
Departamento de Química Biológica and Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Rodríguez-Fermepín
M
M
Vatta
M
M
Fernandez
B E
BE
Rubio
M
M
Peña
C
C
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D005260:Female; D006325:Heart Atria; D007031:Hypothalamus / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase; C118790:angiotensin I (1-7); D009638:Norepinephrine