Pharmacobehavioural evidence for nitric oxide and noradrenaline interactions with ryanodine receptors during memory formation in the young chick.

Inhibiting nitric oxide (NO) synthesis during learning that food is inedible in Aplysia blocks subsequent memory formation. To gain insight into the function of NO transmission during learning we tested whether blocking NO synthesis affects aspects of feeding that are expressed both in a nonlearning context and during learning. Inhibiting NO synthesis with L-NAME and blocking guanylyl cyclase with methylene blue decreased the efficacy of ad libitum feeding. D-NAME had no effect. L-NAME also decreased rejection responses frequency, but did not affect rejection amplitude. The effect of L-NAME was explained by a decreased signaling that efforts to swallow are not successful, leading to a decreased rejection rate, and a decreased ability to reposition and subsequently consume food in ad libitum feeding. Signaling that animals have made an effort to swallow is a critical component of learning that food is inedible. Stimulation of the lips with food alone did not produce memory, but stimulation combined with the NO donor SNAP did produce memory. Exogenous NO at a concentration causing memory also excited a key neuron responding to NO, the MCC. Block of the cGMP second-messenger cascade during training by methylene blue also blocked memory formation after learning. Our data indicate that memory arises from the contingency of three events during learning that food is inedible. One of the events is efforts to swallow, which are signaled by NO by cGMP.

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Demonstrating the dose- and time-related effects of 7-nitroindazole on picrotoxin-induced convulsions, memory formation, brain nitric oxide synthase activity, and nitric oxide concentration in rats

Pharmacology Biochemistry and Behavior ◽

10.1016/j.pbb.2003.08.020 ◽

2004 ◽

Vol 77 (1) ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Paul Vanaja ◽

P. Ekambaram

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Memory Formation ◽

Oxide Concentration ◽

Nitric Oxide Concentration ◽

Oxide Synthase ◽

Brain Nitric Oxide ◽

Nitric Oxide Synthase Activity

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An inhibitor of nitric oxide synthesis prevents memory formation in the chick

Neuroscience Letters ◽

10.1016/0304-3940(92)90012-v ◽

1992 ◽

Vol 145 (2) ◽

pp. 165-167 ◽

Cited By ~ 114

Author(s):

Christian Hölscher ◽

Steven P.R. Rose

Keyword(s):

Nitric Oxide ◽

Memory Formation ◽

Nitric Oxide Synthesis

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Timed and Targeted Differential Regulation of Nitric Oxide Synthase (NOS) and Anti-NOS Genes by Reward Conditioning Leading to Long-Term Memory Formation

Journal of Neuroscience ◽

10.1523/jneurosci.4671-04.2005 ◽

2005 ◽

Vol 25 (5) ◽

pp. 1188-1192 ◽

Cited By ~ 52

Author(s):

S. A. Korneev

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Memory Formation ◽

Differential Regulation ◽

Long Term Memory ◽

Term Memory ◽

Reward Conditioning ◽

Oxide Synthase

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Induction of Hippocampal LTD Requires Nitric-Oxide-Stimulated PKG Activity and Ca2+ Release From Cyclic ADP-Ribose-Sensitive Stores

Journal of Neurophysiology ◽

10.1152/jn.1999.82.3.1569 ◽

1999 ◽

Vol 82 (3) ◽

pp. 1569-1576 ◽

Cited By ~ 76

Author(s):

Magali Reyes-Harde ◽

Barry V. L. Potter ◽

Antony Galione ◽

Patric K. Stanton

Keyword(s):

Nitric Oxide ◽

Guanylyl Cyclase ◽

Ryanodine Receptors ◽

Low Frequency ◽

Calcium Stores ◽

No Donor ◽

Cyclic Adp Ribose ◽

Dependent Form ◽

Frequency Stimulation

Long-term depression (LTD) of synaptic transmission can be induced by several mechanisms, one thought to involve Ca2+-dependent activation of postsynaptic nitric oxide (NO) synthase and subsequent diffusion of NO to the presynaptic terminal. We used the stable NO donor S-nitroso- N-acetylpenicillamine (SNAP) to study the NO-dependent form of LTD at Schaffer collateral-CA1 synapses in vitro. SNAP (100 μM) enhanced the induction of LTD via a cascade that was blocked by the N-methyl-d-aspartate receptor antagonist d-2-amino-5-phosphonopentanoic acid (50 μM), NO guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (10 μM), and the PKG inhibitor KT5823 (1 μM). We further show that LTD induced by low-frequency stimulation in the absence of SNAP also is blocked by KT5823 or Rp-8-(4-chlorophenylthio)-guanosine 3′,5′-cyclic monophosphorothioate (10 μM), cyclic guanosine 3′,5′ monophosphate-dependent protein kinase (PKG) inhibitors with different mechanisms of action. Furthermore SNAP-facilitated LTD was blocked when release from intracellular calcium stores was inhibited by ryanodine (10 μM). Finally, two cell-permeant antagonists of the cyclic ADP-ribose binding site on ryanodine receptors also were able to block the induction of LTD. These results support a cascade for induction of homosynaptic, NO-dependent LTD involving activation of guanylyl cyclase, production of guanosine 3′,5′ cyclic monophosphate and subsequent PKG activation. This process has an additional requirement for release of Ca2+ from ryanodine-sensitive stores, perhaps dependent on the second-messenger cyclic ADP ribose.

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Nitric oxide inhibits calcium release from sarcoplasmic reticulum of porcine tracheal smooth muscle cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.272.1.l1 ◽

1997 ◽

Vol 272 (1) ◽

pp. L1-L7 ◽

Cited By ~ 14

Author(s):

M. S. Kannan ◽

Y. S. Prakash ◽

D. E. Johnson ◽

G. C. Sieck

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Sarcoplasmic Reticulum ◽

Calcium Release ◽

Ryanodine Receptors ◽

Tracheal Smooth Muscle ◽

Nitric Oxide Donor ◽

Ip3 Receptors ◽

Video Fluorescence Microscopy ◽

Inositol 1,4,5 Trisphosphate

In the present study, effects of the nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP), on sarcoplasmic reticulum (SR) Ca2+ release were examined in freshly dissociated porcine tracheal smooth muscle (TSM) cells. Fura 2-loaded TSM cells were imaged using video fluorescence microscopy. SR Ca2+ release was induced by acetylcholine (ACh), which acts principally through inositol 1,4,5-trisphosphate (IP3) receptors, and by caffeine, which acts principally through ryanodine receptors (RyR). SNAP inhibited ACh-induced SR Ca2+ release at both 0 and 2.5 mM extracellular Ca2+. Degraded SNAP had no effect on ACh-induced SR Ca2+ release. SNAP also inhibited caffeine-induced SR Ca2+ release. ACh-induced Ca2+ influx was not affected by SNAP when SR reloading was blocked by thapsigargin. SNAP also did not affect SR Ca2+ reuptake. The membrane-permeant analogue of guanosine 3',5'-cyclic monophosphate (cGMP), 8-bromo-cGMP, mimicked the effects of SNAP. These results suggest that, in porcine TSM cells, SNAP reduces the intracellular Ca2+ response to ACh and caffeine by inhibiting SR Ca2+ release through both IP3 and RyR, but not by inhibiting influx or repletion of the SR Ca2+ stores. These effects are likely mediated via cGMP-dependent mechanisms.

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Involvement of Nitric Oxide in Iodine Deficiency-Induced Microvascular Remodeling in the Thyroid Gland: Role of Nitric Oxide Synthase 3 and Ryanodine Receptors

Endocrinology ◽

10.1210/en.2014-1729 ◽

2014 ◽

Vol 156 (2) ◽

pp. 707-720 ◽

Cited By ~ 13

Author(s):

J. Craps ◽

C. Wilvers ◽

V. Joris ◽

B. De Jongh ◽

J. Vanderstraeten ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Thyroid Gland ◽

Mrna Expression ◽

Iodine Deficiency ◽

Ryanodine Receptors ◽

No Production

Iodine deficiency (ID) induces microvascular changes in the thyroid gland via a TSH-independent reactive oxygen species-hypoxia inducible factor (HIF)-1α-vascular endothelial growth factor (VEGF) pathway. The involvement of nitric oxide (NO) in this pathway and the role of calcium (Ca2+) and of ryanodine receptors (RYRs) in NO synthase 3 (NOS3) activation were investigated in a murine model of goitrogenesis and in 3 in vitro models of ID, including primary cultures of human thyrocytes. ID activated NOS3 and the production of NO in thyrocytes in vitro and increased the thyroid blood flow in vivo. Using bevacizumab (a blocking antibody against VEGF-A) in mice, it appeared that NOS3 is activated upstream of VEGF-A. L-nitroarginine methyl ester (a NOS inhibitor) blocked the ID-induced increase in thyroid blood flow in vivo and NO production in vitro, as well as ID-induced VEGF-A mRNA and HIF-1α expression in vitro, whereas S-nitroso-acetyl-penicillamine (a NO donor) did the opposite. Ca2+ is involved in this pathway as intracellular Ca2+ flux increased after ID, and thapsigargin activated NOS3 and increased VEGF-A mRNA expression. Two of the 3 known mammalian RYR isoforms (RYR1 and RYR2) were shown to be expressed in thyrocytes. RYR inhibition using ryanodine at 10μM decreased ID-induced NOS3 activation, HIF-1α, and VEGF-A expression, whereas RYR activation with ryanodine at 1nM increased NOS3 activation and VEGF-A mRNA expression. In conclusion, during the early phase of TSH-independent ID-induced microvascular activation, ID sequentially activates RYRs and NOS3, thereby supporting ID-induced activation of the NO/HIF-1α/VEGF-A pathway in thyrocytes.

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