Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation

Zhuo, Min; Hu, Yinghe; Schultz, Carsten; Kandel, Eric R.; Hawkins, Robert D.

doi:10.1038/368635a0

Cited by 414 publications

(273 citation statements)

References 23 publications

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“…Zaprinast (10 mM), a selective inhibitor of type V (cyclic GMP speci®c) phosphodiesterase (Lugnier et al, 1986), potentiated the relaxant e ects of YC-1 (Figure 1b). Rp-8-Br-cGMPs, a cyclic GMP analogue that inhibits protein kinase G (Zhuo et al, 1994), antagonized the relaxant e ects of YC-1 (Figure 1b). The EC 50 values of YC-1 were 2.9 mM under control conditions, 0.7 mM in the presence of zaprinast (10 mM) and 5.6 mM in the presence of Rp-8-Br-cGMPS (100 mM).…”

Section: E Ects Of Yc-1 On Aortic Tensionmentioning

confidence: 99%

Activation of soluble guanylyl cyclase by YC‐1 in aortic smooth muscle but not in ventricular myocardium from rat

Wegener

Gath

Förstermann

et al. 1997

British J Pharmacology

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1 The e ects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole), an activator of soluble guanylyl cyclase, on tension, levels of cyclic GMP and cyclic AMP, and cardiac L-type Ca 2+ -current (I Ca(L) ) were investigated in aortic smooth muscle and ventricular heart muscle from rat. 2 YC-1 (0.1 ± 30 mM) induced a concentration-dependent relaxation in aortic rings precontracted with phenylephrine (3 mM). The relaxant e ects of YC-1 were reversed by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (30 mM; ODQ), potentiated by zaprinast (10 mM) and antagonized by Rp-8-BrcGMPS (100 mM). 3 In ventricular heart muscle strips, YC-1 (30 mM) exhibited no e ects on force of contraction (F c ) in the absence or presence of either zaprinast (10 mM) or 3-isobutyl-1-methylxanthine (30 mM). F c was slightly increased by YC-1 (30 mM) in the presence of isoprenaline (100 nM), but this e ect was not in¯uenced by ODQ (30 mM). 4 Cardiac I Ca(L) was not signi®cantly a ected by YC-1 (30 mM), either in the absence or presence of isoprenaline (30 nM). 5 In aortic rings, cyclic GMP levels were increased almost 3 fold by YC-1 (30 mM); this e ect was abolished by ODQ (30 mM). In isolated ventricular cardiomyocytes, cyclic GMP levels were not a ected by YC-1 (30 mM) but almost doubled by activation of particular guanylyl cyclase with atriopeptin II (100 nM). 6 YC-1 (30 mM) did not increase cyclic AMP levels either in aortic rings or in ventricular cardiomyocytes. In contrast, isoprenaline (3 mM) increased cyclic AMP levels about two fold in both tissues. In cardiomyocytes, the e ect of isoprenaline (3 mM) was slightly enhanced by YC-1 (30 mM). 7 It is concluded that relaxation of smooth muscle preparations by YC-1 is mediated mainly by activation of soluble guanylyl cyclase and subsequent increase in cyclic GMP levels. The failure of YC-1 to a ect cardiac F c , levels of cyclic GMP, and I Ca(L) suggests that soluble guanylyl cyclase is not in¯uenced by YC-1 in rat heart muscle or only barely present in this tissue.

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Section: E Ects Of Yc-1 On Aortic Tensionmentioning

confidence: 99%

Activation of soluble guanylyl cyclase by YC‐1 in aortic smooth muscle but not in ventricular myocardium from rat

Wegener

Gath

Förstermann

et al. 1997

British J Pharmacology

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“…These studies have largely relied on intracellular application of PKG or make use of the newly developed PKG agonist 8-(pchlorophenylthio)cGMP (8-pCPT-cGMP) or antagonist Rp-8-bromoguanosine 31,5 '-cyclic monophosphothioate, both of which are largely without effects on PDEs or cGMP-gated ion channels. These neuronal effects of PKG include direct roles in regulation of neuronal Ca2~currents (Meriney et al, 1994), control of neuronal firing rates or neurotransmitter release (Woody et al, 1986;Branisteanu et al, 1988;Akamatsu et al, 1993;Pineda et al, 1996), as the presynaptic target for the retrograde messenger in LTP (Zhuo et al, 1994;Arancio et al, 1995), and in the activation of neuronal K~channels (Furukawa et al, 1996). Other direct effects of PKG on cellular function have also been determined in nonneuronal cells that may be of relevance to the brain (for review, see ; also see below).…”

Section: Role Of Pkg In Neurotransmissionmentioning

confidence: 99%

“…LTP in chick ciliary ganglia is mimicked by cGMP analogues at the initiation or maintenance phase of LTP (Lin and Bennett, 1994). Zhuo et al (1994) have shown that a GC inhibitor blocks the induction of LTP in the CAl region of hippocampal slices. Conversely, cGMP analogues produce long-lasting enhancement of the excitatory postsynaptic potential, associated with an increase in PKG activity.…”

Section: Ltp and Long-term Depression (Ltd)mentioning

confidence: 99%

“…Effects in cultured neurons may be attributed to effects within single cells or local interactions between related cells (Hirsch et al, 1993;Meriney eta!., 1994). However, effects in brain slices may relate to complex interactions between nerve cells and glia and cannot easily be attributed to the direct action of cGMP in nerve endings (Lonart et al, 1993;Zhuo et al, 1994). Therefore, direct molecular mechanisms of cGMP action may best be studied in single cell or subcellular models.…”

Section: Modulation Of Neurotransmitter Releasementioning

confidence: 99%

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Cyclic GMP‐Dependent Protein Kinase and Cellular Signaling in the Nervous System

Wang

Robinson

1997

Journal of Neurochemistry

264

128

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Nitric oxide (NO) and natriuretic peptide hormones play key roles in a surprising number of neuronal functions, including learning and memory. Most data suggest that they exert converging actions by elevation of intracellular cyclic GMP (cGMP) levels through activation of soluble and particulate guanylyl cyclases. However, cGMP is only the starting point for multiple signaling cascades, which are now beginning to be defined. A primary action of elevated cGMP levels is the stimulation of cGMP-dependent protein kinase (PKG), the major intracellular receptor protein for cGMP, which phosphorylates substrate proteins to exert its actions. It has become increasingly clear that PKG mediates some of the neuronal effects of cGMP, but how is not yet clear. One clear illustration of this pathway has been reported in striatonigral nerve terminals, where NO mediates phosphorylation of the protein phosphatase regulator dopamine-and cyclic AM P-regulated phosphoprotein having a molecular mass of 32,000 (DARPP-32) by PKG. There are remarkably few PKG substrates in brain whose identities are known. A survey of these proteins and those known from other tissues that might also be found in the nervous system reveals the key molecular sites where cGMP and PKG signaling is likely to be regulating neural function. These potential substrates are critically placed to have profound effects on the protein phosphorylation network through regulation of protein phosphatases, intracellular calcium levels, and the function of many ion channels and neurotransmitter receptors. The brain also contains a rich diversity of specific PKG substrates whose identities are not yet known. Their future identification will provide exciting new leads that will permit better understanding of the role of PKG signaling in both basic and higher orders of brain function. Key Words: Protein phosphorylation-Cyclic GMP-Cyclic GMP-dependent protein kinase-BrainNeuron-Neurotransmitter release. J. Neurochem. 68, 443-456 (1997).The widespread biological importance of cyclic GMP (cGMP) signaling through cGMP-dependent protein kinase (PKG) has been slow to be appreciated. Despite an exciting flourish of activity in the late I 960s and early 1970s when both cGMP and PKG were discovered, research largely languished for many years and was focused in only a small number of laboratories. This was probably due to the difficulty in determining how this signaling system was activated, what biological processes it regulated, and what substrates of PKG might mediate its actions. PKG' s role in smooth muscle relaxation has been the most significant area of productive research. It was not until more recent years that it was discovered that two pathways lead to cGMP signaling, via natriuretic peptides such as atrial natriuretic peptide (ANP) and soluble gases such as nitric oxide (NO) and carbon monoxide, which elevate intracellular cGMP levels through activation of particulate (GC-P) and soluble (GC-S) guanylyl cyclases (Fig. 1). In the last few years there has been an expl...

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“…However, despite the fact that the NO-coupled cyclic GMP pathway has a widespread anatomical distribution in the mammalian brain (Bredt et al, 1990;Förstermann et al, 1990;Furuyama et al, 1993;Burgunder and Cheung, 1994), its functions are not well understood. One hypothesized function is the modulation of synaptic strength, 1651 both in the immature brain, when developmental programs specify the survival and elimination of specific synapses Wu et al, 1994;Ogilvie et al, 1995;Wallhausser-Franke et al, 1995;Wang et al, 1995;Wetts et al, 1995;lentile et al, 1996), and in the mature brain, when certain types of neural activity induce long-term (Daniel et al, 1993;Hartell, 1994;Zhuo et al, 1994;Arancio et al, 1995;Boulton et al, 1995;Boxall and Garthwaite, 1996) or transient (Boulton et al, 1994;Broome et al, 1994) changes in synaptic efficacy.…”

mentioning

confidence: 99%

Identification of Nitric Oxide‐Sensitive and ‐Insensitive Forms of Cytoplasmic Guanylate Cyclase

Prabhakar

Short

Scholz

et al. 1997

Journal of Neurochemistry

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Cytoplasmic, nitric oxide-activated guanylate cyclases are expressed in many regions of the mammaian brain and are thought to participate in functions as diverse as synaptogenesis and long-term potentiation. In this study, we have characterized cytoplasmic guanylate cyclases in the nervous system of an invertebrate, the American lobster. Cytoplasmic cyclase specific activity is higher in lobster nerve cord than in any other lobster tissue tested, and considerably higher than in typical rat tissues (cerebellum, lung, and liver). However, nitric oxide donors have minimal effects on lobster nerve cord cyclic GMP production, when applied either to intact tissue or to cytoplasmic extracts. Parallel immunocytochemical studies, using an anti-cyclic GMP antibody, reveal that only a small subset of lobster neurons responds to nitric oxide with a significant elevation of cyclic GMP levels. HPLC analysis of nerve cord cytoplasm reveals two chromatographically separable cyclases, a minor nitric oxide-sensitive form whose retention time is identical to that of the conventional mammalian enzyme and a more abundant nitric oxide-insensitive form that appears to be novel. The physiological function and phylogenetic distribution of this nitric oxide-insensitive enzyme, and the signaling mechanisms that regulate its activity, are not known.

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Role of guanylyl cyclase and cGMP-dependent protein kinase in long-term potentiation

Cited by 414 publications

References 23 publications

Activation of soluble guanylyl cyclase by YC‐1 in aortic smooth muscle but not in ventricular myocardium from rat

Activation of soluble guanylyl cyclase by YC‐1 in aortic smooth muscle but not in ventricular myocardium from rat

Cyclic GMP‐Dependent Protein Kinase and Cellular Signaling in the Nervous System

Identification of Nitric Oxide‐Sensitive and ‐Insensitive Forms of Cytoplasmic Guanylate Cyclase

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