Atrial natriuretic factor inhibits norepinephrine biosynthesis and turnover in the rat hypothalamus.
We have previously reported that atrial natriuretic factor (ANF) increased neuronal norepinephrine (NE) uptake and reduced basal and evoked neuronal NE release. Changes in NE uptake and release are generally associated to modifications in the synthesis and/or turnover of the amine. On this basis, the aim of the present work was to study ANF effects in the rat hypothalamus on the following processes: endogenous content, utilization and turn-over of NE; tyrosine hydroxylase (TH) activity; cAMP and cGMP accumulation and phosphatidylinositol hydrolysis. Results showed that centrally applied ANF (100 ng/microl/min) increased the endogenous content of NE (45%) and diminished NE utilization. Ten nM ANF reduced the turnover of NE (53%). In addition, ANF (10 nM) inhibited basal and evoked (with 25 mM KCl) TH activity (30 and 64%, respectively). Cyclic GMP levels were increased by 10 nM ANF (100%). However, neither cAMP accumulation nor phosphatidylinositol breakdown were affected in the presence of 10 nM ANF. The results further support the role of ANF in the regulation of NE metabolism in the rat hypothalamus. ANF is likely to act as a negative putative neuromodulator inhibiting noradrenergic neurotransmission by signaling through the activation of guanylate cyclase. Thus, ANF may be involved in the regulation of several central as well as peripheral physiological processes such as cardiovascular function, electrolyte and fluid homeostasis, endocrine and neuroendocrine synthesis and secretion, behavior, thirst, appetite and anxiety that are mediated by central noradrenergic activity.
Vatta
M S
MS
Cátedras de Fisiología y Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina. mvatta@ffyb.uba.ar
Rodríguez-Fermepín
M
M
Durante
G
G
Bianciotti
L G
LG
Fernández
B E
BE
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000096:biosynthesis* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism
D010716:Phosphatidylinositols; C472610:atrial natriuretic peptide, rat; D011189:Potassium Chloride; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D009638:Norepinephrine