Nitric oxide inhibits the release of norepinephrine and dopamine from the medial basal hypothalamus of the rat.

Abstract

Previous research indicates that norepinephrine and dopamine stimulate release of luteinizing hormohe (LH)-releasing hormone (LHRH), which then reaches the adenohypophysis via the hypophyseal portal vessels to release LH. Norepinephrine exerts its effect via ol-adrenergic receptors, which stimulate the release of nitric oxide (NO) from nitricoxidergic (NOergic) neurons in the medial basal hypothalamus (MBH). The NO activates guanylate cyclase and cyclooxygenase, thereby inducing release of LHRH into the hypophyseal portal vessels. We tested the hypothesis that these two catecholamines modulate NO release by local feedback. MBH explants were incubated in the presence of sodium nitroprusside (NP), a releaser of NO, and the effect on release of catecholamines was determined. NP inhibited release of norepinephrine. Basal release was increased by incubation of the tissue with the NO scavenger hemoglobin (20 ,ig/ml).Hemoglobin also blocked the inhibitory effect of NP. In the presence of high-potassium (40 mM) medium to depolarize cell membranes, norepinephrine release was increased by a factor of 3, and this was significantly inhibited by NP. Hemoglobin again produced a further increase in norepinephrine release and also blocked the action of NP. When constitutive NO synthase was inhibited by the competitive inhibitor NG-monomethyl-L-arginine (NMMA) at 300 ,iM, basal release of norepinephrine was increased, as was potassium-evoked release, and this was associated in the latter instance with a decrease in tissue concentration, presumably because synthesis did not keep up with the increased release in the presence of NMMA. The results were very similar with dopamine, except that reduction of potassium-evoked dopamine release by NP was not significant. However, the increase following incubation with hemoglobin was significant, and hemoglobin, when incubated with NP, caused a significant elevation in dopamine release above that with NP alone. In this case, NP increased tissue concentration of dopamine along with inhibiting release, suggesting that synthesis continued, thereby raising the tissue concentration in the face of diminished release. When the tissue was incubated with NP plus hemoglobin, which caused an increase in release above that obtained with NP alone, the tissue concentration decreased significantly compared with that in the absence of hemoglobin, indicating that, with increased release, release exceeded synthesis, causing a fall in tissue concentration. When NO synthase was blocked by NMMA, the release of dopamine, under either basal or potassium-evoked conditions, was increased. Again, in the latter instance the tissue concentration declined significantly, presumably because synthesis did not match release. Therefore, the results were very similar with both catecholamines and indicate that NO acts to suppress release of both amines. Since both catecholamines activate the release of LHRH, the inhibition of their release by NO serves as an ultra-short-loop negative feedback by which NO inhibits the ...

Kalirin Inhibition of Inducible Nitric-oxide Synthase

“…The fact that LPS and interferon treatment inhibits basal and stimulated ACTH secretion from AtT-20 cells is consistent with other studies which show that NO inhibits ACTH secretion (27)(28)(29)(30)(31)(32)(33)(34)(35)(36). The effect of LPS upon the pituitary is complex: in the whole animal LPS is often reported to stimulate ACTH secretion (87).…”

“…Experimental evidence from neuronal cultures and animal models shows that NO can also inhibit specific secretory responses of neurons. For example, some but not all modes of stimulating hormone secretion from the pituitary are enhanced in the presence of NOS inhibitors (27)(28)(29)(30)(31)(32)(33)(34)(35)(36).…”

Distribution of NADPH-Diaphorase-Positive Neurons in the Mouse Brain: Differences from Previous Findings in the Rat Brain and Comparison with the Distribution of Serotonergic Neurons.

“…Some studies have suggested an interaction between NO and other neurotransmitters such as dopamine (DA) [18,28,37,51], noradrenaline [51], GABA [63], acetylcholine (Ach) [56,62] and 5-HT [11,23,38,66]. In the medial preoptic area, NO has been shown by a microdialysis method to increase 5-HT and DA levels [38].…”

The role of nitric oxide in reproduction

“…We have already described the ability of NE to stimulate LHRH release and the fact that dopamine also acts as a stimulatory transmitter in the pathway. Therefore, there is an ultra short-loop negative feedback mechanism to terminate the pulsatile release of LHRH since the NO released by NE would diffuse to the noradrenergic terminals and inhibit the release of NE, thereby terminating the pulse of NE, LHRH and finally LH (24).…”