Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spatial and temporal distribution of soluble guanylyl cyclase and nitric oxide synthase mRNA was determined during embryonic and postnatal development of the mouse brain. This was achieved by in situ hybridization of specific probes for soluble beta 1 guanylyl cyclase subunit and nitric oxide synthase mRNA on mouse brain sections at late fetal development (19-day embryo) and different stages of postnatal development (3, 7, 15 days, and adult). In the embryo, soluble guanylyl cyclase transcripts are weakly expressed in the central nervous system. Following birth their expression increases in the striatum and neocortex, and they are widely distributed in the adult brain (layer II and V-VI of the cortex, olfactory bulb, striatum, Purkinje cell layer of the cerebellum). In contrast, nitric oxide synthase mRNA was expressed in several embryonic structures of the brain (different layers of the cortical neuroepithelium, colliculi neuroepithelium, pons), and markedly reduced at early postnatal stage, except in the accessory olfactory bulb and pediculopontine nuclei. Nitric oxide synthase transcripts progressively appear, within two weeks following birth, in the striatum and the cerebral cortex but they were specifically confined to isolated cells. During this period, this mRNA also increased in hippocampus, in discrete nuclei (hypothalamus, pontine) and in the molecular layer of the cerebellum. The situation in the adult was similar to the one observed at 15 days. These results show a general lack of regional colocalization of soluble guanylyl cyclase and NOS mRNA during ontogeny, thus suggesting an independent regulation of the related genes.
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PMID:Expression of mouse brain soluble guanylyl cyclase and NO synthase during ontogeny. 752 43

Two isoforms of the enzyme heme oxygenase are expressed in distinct populations of neurons in the brain. These enzymes catalyse the oxidative cleavage of heme to the cellular antioxidant biliverdin resulting in the release of carbon monoxide in the process. Both heme and carbon monoxide may play important roles in regulating the nitric oxide-cyclic guanosine monophosphate signal transduction system. Thus we have examined the distributions of both isoforms of heme oxygenase in the rat brain, and compared their localizations with that of nitric oxide synthase determined with the NADPH-diaphorase histochemical technique. Heme oxygenase-1 is highly expressed in a few select populations of neurons including cells in the hilus of the dentate gyrus, in the hypothalamus, cerebellum and brainstem. This enzyme appears to be coexpressed with nitric oxide synthase only in a few cells in the dentate gyrus. Heme oxygenase-2 is much more widely expressed. It is present in mitral cells in the olfactory bulb, pyramidal cells in the cortex and hippocampus, granule cells in the dentate gyrus, many neurons in the thalamus, hypothalamus, cerebellum and caudal brainstem. However, only some of these labelled neurons also displayed nitric oxide synthase. Instead, many neurons expressing heme oxygenase-2 correspond to those known to express high levels of the hemoprotein soluble guanylyl cyclase. These results suggest that heme oxygenase may play a role in modulating guanylyl cyclase independent of nitric oxide synthase. This may result from regulation of intracellular heme and carbon monoxide levels by the heme oxygenase system.
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PMID:Brain heme oxygenase isoenzymes and nitric oxide synthase are co-localized in select neurons. 753 81

Carbon monoxide, an activator of guanylyl cyclase, is formed by the action of the enzyme heme oxygenase. By in situ hybridization in brain slices, discrete neuronal localization of messenger RNA for the constitutive form of heme oxygenase throughout the brain has been demonstrated. This localization is essentially the same as that for soluble guanylyl cyclase messenger RNA. In primary cultures of olfactory neurons, zinc protoporphyrin-9, a potent selective inhibitor of heme oxygenase, depletes endogenous guanosine 3',5'-monophosphate (cGMP). Thus, carbon monoxide, like nitric oxide, may be a physiologic regulator of cGMP. These findings, together with the neuronal localizations of heme oxygenase, suggest that carbon monoxide may function as a neurotransmitter.
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PMID:Carbon monoxide: a putative neural messenger. 809 63

The rapid and transient generation of pulses of either cAMP or IP3 is considered the primary reaction in olfactory signal transduction. There is some recent evidence suggesting that another second messenger system, involving cGMP, may also play an important role in olfactory signalling. High doses of odorant elicit a delayed and sustained elevation of cGMP levels due to the operation of the nitric oxide (NO) synthase/guanylyl cyclase system. The interplay of NO and cGMP is supposed to trigger molecular mechanisms, including adaptation processes, which enable the olfactory neuroepithelium to cope with strong stimuli. Furthermore, a characteristic pattern of staining for NO synthase in the olfactory bulb suggests that the NO/cGMP system may also participate in neuronal processing of the sensory input.
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PMID:Implications of the NO/cGMP system for olfaction. 767 37

Nitric oxide (NO) is a free radical that has been recently recognized as a neuronal messenger molecule. In order to understand the way in which NO functions in the central nervous system (CNS), it is important to identify the NO-generator and NO-target cells in the brain. I measured firstly the distribution of NO synthase in the brain, which catalyzes L-arginine to form NO, by the measurement of citrulline formation that is also synthesized from L-arginine together with NO in equal molar bass. In the brain of adult rat, the most potent activity of NOS was apparent in the cerebellum, next in the olfactory bulb and medium in the cerebrum. Further, in the presence of NADPH and Ca2+, NOS activity was detected in the neuron cultures derived from the cerebrum of fetal rat. Astrocytes, one type of glia, prepared also from the cerebrum of fetal rat, appeared to have a small but significant NOS activity. As astrocytes possess a high amount of cytosolic guanylate cyclase that is known to be activated by NO, the changes in the intracellular cGMP levels in the astrocytes were measured as another index of NO formation. The treatment of astrocytes with NOS inhibitor caused the suppression of the intracellular cGMP levels. These results indicate that NO is definitely produced by astrocytes. In addition, in the blood vessel system of the brain, although NOS has been thought to be localized in the endothelial cells of only larger vessels, NOS activity was also observed in the microvessel endothelial cells of the cerebrum of both adult and fetal pig. These data suggest that neuronal cells may be the major site of NO generation in the brain, and that the NOS is a constitutive type. The data also suggest that astrocytes can also express constitutive NOS, although the potency is not so large. Microvessel endothelial cells of the brain are also one of the sources of NO. The NO produced by these cells increases the cGMP levels in the astrocytes and may affect some physiological and/or pathophysiological events in the brain.
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PMID:Evidence for nitric oxide-generator cells in the brain. 769 25

We have cloned an additional member (GC-D) of the membrane receptor guanylyl cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] family that is specifically expressed in a subpopulation of olfactory sensory neurons. The extracellular, putative ligand-binding domain of the olfactory cyclase is similar in primary structure to two guanylyl cyclases expressed in the retina but diverges considerably from other known guanylyl cyclases. The expression of GC-D RNA is restricted to a small, randomly dispersed population of neurons that is within a single topographic zone in the olfactory neuroepithelium and resembles the pattern of the more diverse seven-transmembrane-domain odorant receptors. These observations suggest that GC-D may function directly in odor recognition or in modulating the sensitivity of a subpopulation of sensory neurons to specific odors.
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PMID:A receptor guanylyl cyclase expressed specifically in olfactory sensory neurons. 772

We applied reverse transcription-PCR to examine the gene expression of cyclic GMP (cGMP)-dependent protein kinase in the rat brain. A PCR product with the size predicted from the type II cGMP-dependent protein kinase (cGK II) cDNA was detected in various regions of the brain, with highest expression in the thalamus. The amplified product of this cDNA was subcloned, sequenced, and consequently shown to be cGK II. Northern analysis confirmed that this kinase was highly expressed in the thalamus. In situ hybridization with riboprobes derived from this cDNA indicated that cGK II mRNA was highly expressed in the outer layers of the cortex, the septum, amygdala, and olfactory bulb with highest levels in the thalamus. High amounts of cGK II mRNA were also found in specific brainstem loci, including the medial habenula, the subthalamic nucleus, the locus ceruleus, the pontine nucleus, the inferior olivary nuclei, and the nucleus of the solitary tract. Only low levels of cGK II mRNA were detected in the striatum, cerebellum, and hippocampus. These data suggest that the effects of guanylyl cyclase activators, such as nitric oxide and the atriopeptides, in various regions of the CNS may be mediated through cGK II.
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PMID:Molecular characterization of a type II cyclic GMP-dependent protein kinase expressed in the rat brain. 776 63

The cDNAs for two membrane guanylyl cyclases, designated E (GC-E) and F (GC-F, were isolated from a rat eye cDNA library. Their deduced topographic structures correspond to known members of the guanylyl cyclase receptor family, containing an extracellular domain, a single membrane-spanning domain, a protein kinase-like domain, and a cyclase catalytic domain. GC-E was expressed in the eye and the pineal gland, whereas GC-F expression was confined to the eye. Overproduction of GC-E and GC-F in COS cells resulted in expression of guanylyl cyclase activity, but ligands known to activate other guanylyl cyclase receptors failed to stimulate enzyme activity. Thus, both GC-E and GC-F remain orphan receptors. Amino acid sequence similarity between GC-E and GC-F in the extracellular region and homology with a cyclase expressed in olfactory neurons and retGC, a rod outer-segment-specific cyclase, suggest that there is another subfamily of guanylyl cyclase receptors, possibly restricted to sensory tissues.
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PMID:Two membrane forms of guanylyl cyclase found in the eye. 783 37

The ultracytochemical localization of particulate guanylate cyclase has been studied in lamb olfactory mucosa after activation with rat atrial natriuretic factor (rANF), porcine brain natriuretic peptide (pBNP), porcine C-type natriuretic peptide (pCNP) or rat brain natriuretic peptide (rBNP). Particulate guanylate cyclase is the receptor for these peptides and recently two subtypes of the cyclase have been identified. These isoforms are stimulated differently by ANF, BNP and CNP. Under our experimental conditions, rANF, pCNP and pBNP were strong activators of particulate guanylate cyclase in lamb olfactory mucosa, as demonstrated by the presence of reaction product. Samples incubated in basal conditions without rANF, pCNP or pBNP, or samples incubated in presence of rBNP did not reveal any cyclase activity. The rANF-stimulated cyclase activity was localized in the apical portion of olfactory epithelium. pCNP-stimulated guanylate cyclase was detected to the lamina propria in association with secretory cells of Bowman's glands and with cells in close relation with Bowman's glands (elongated cells and myoepithelial cells). The cyclase activity stimulated by pBNP was limited to cells of Bowman's glands. The present data indicate that ANF and CNP are recognized by different receptors and that BNP and CNP bind to the same receptor.
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PMID:Ultracytochemical localization of particulate guanylate cyclase after stimulation with natriuretic peptides in lamb olfactory mucosa. 788 88

Atrial natriuretic peptide (ANP) or an Atriopeptin III analog (PL 058) stimulated cGMP formation in the membrane fraction of rat olfactory bulb, median eminence and paraventricular nucleus, in a dose-dependent manner. The effect of the Atriopeptin III analog was 20-40% greater than that of ANP. Bilateral adrenalectomy, with or without mineralo- or glucocorticoid-replacement, on ANP-stimulated cGMP formation was investigated in rat paraventricular nucleus. 11 days after bilateral adrenalectomy a reduced responsiveness to ANP- or PL 058-induced cGMP production was observed. This effect was prevented by deoxycorticosterone, but not by dexamethasone administration. Our results further support the presence of guanylate cyclase-coupled ANP receptors in brain localized target sites; and they provide evidence suggesting that guanylate cyclase-linked ANP binding sites in the PVN are susceptible to regulatory changes after adrenalectomy-induced activation of the hypothalamus-hypophyso-adrenocortical system.
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PMID:Adrenalectomy reduces atrial natriuretic peptide stimulated guanylate cyclase activity in rat paraventricular nucleus. 790 81


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