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

---

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

The role of nitric oxide (NO) in the activity of cyclooxygenase (COX) in cultured canine tracheal epithelium was studied. Tracheal epithelium spontaneously released prostaglandin E2 (PGE2), which is a product of COX. The release of PGE2 was increased by bradykinin and was decreased by two NO synthase inhibitors: NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine. That decrease was reversed in the presence of L-arginine. Chrolpromadin, but not aminoguanidine, inhibited PGE2 production, which suggests that constitutive NO synthase is involved. Two stable NO donors, sodium nitroprusside and S-nitroso-N-acetyl DL-penicillamine, also increased the production of PGE2. These effects were abolished by coincubation with hemoglobin, which binds and inactivates NO, but not by methylene blue, an inhibitor of soluble guanylate cyclase. NADPH diaphorase histochemistry of cultured tracheal cells revealed activity in the periphery of the cytoplasm. These results suggest that, in cultured canine tracheal epithelium, NO directly interacts with COX to regulate PGE2 production.
...
PMID:[Regulation of cyclooxygenase activity in airway epithelium by endogenous nitric oxide]. 874 27

The present study attempts to review presently known data regarding the distribution of nitric oxide (NO) synthase and the function of NO in invertebrate species. NO is synthesized from L-arginine by the enzyme NO-synthase, and activates guanylate cyclase which in turn leads to an increase in levels of cGMP in target cells. Major contributions to the knowledge of NO as a messenger molecule in invertebrates have been made by NADPH-diaphorase histochemistry and biochemical assays. These techniques suggest the presence of a L-arginine/NO pathway in a variety of tissues, thus implicating multiple roles for NO in invertebrates.
...
PMID:NO-synthase: what can research on invertebrates add to what is already known? 874 15

The aim of this study was to investigate the involvement of nitric oxide (NO) in the nonadrenergic, noncholinergic (NANC) relaxation of the urinary bladder of the Atlantic cod, Gadus morhua. NADPH diaphorase-reactive nerve cells, presumed to be able to produce NO, were found in the vesicular nerve. The cells occurred alone and in ganglia together with stained and unstained cells. The effect of inhibitors of NO synthesis on the relaxation was examined in vitro in isolated muscle preparations. NG-nitro-L-arginine methyl ester (10(-4) M) and NG-nitro-L-arginine (L-NNA; 10(-4) M) decreased the electrically induced relaxation to 32 +/- 6 (n = 8) and 28 +/- 6% (n = 8) of the control, respectively. L-Arginine (10(-3) M) increased the relaxation to 152 +/- 24% (n = 8), without affecting the inhibition by L-NNA. The beta-adrenoceptor antagonist propranolol together with L-arginine analogues abolished the relaxation in 7 of 11 preparations. The NO donor sodium nitroprusside (NaNP) caused a concentration-dependent relaxation of the bladder, with a maximal effect obtained at 10(-4) M. LY-83583 (10(-5) M), a guanylate cyclase inhibitor, decreased both the electrically (n = 8) and the NaNP (10(-6) M, n = 9)-induced relaxation to 69 +/- 5 and 20 +/- 4% of the control, respectively. Together these findings suggest that NO is involved in the NANC regulation of the motility of the urinary bladder of the Atlantic cod.
...
PMID:Involvement of nitric oxide in inhibitory innervation of urinary bladder of Atlantic cod, Gadus morhua. 876 7

Recent studies suggest that nitric oxide (NO) may function as a neurotransmitter in the hypothalamus. In order to provide further evidence supporting this contention, we examined: (1) whether the hypothalamus displays significant NO synthase (NOS) activity and whether the activity is inhibited by an NOS inhibitor, (2) whether the different NOS isoforms [brain (b)-NOS, endothelial (e)-NOS and macrophage (m)-NOS] are expressed in the various nuclei of the hypothalamus of the random cycling adult female rat, (3) whether the NO donor molecule, sodium nitroprusside (SNP), regulates the heme-containing enzyme, guanylate cyclase in the preoptic area and medial basal hypothalamus of the random cycling adult female rat as well as the ovariectomized steroid (estradiol-17 beta)-treated rat. The results of the study showed that the preoptic area (POA) and medial basal hypothalamus (MBH) of the adult female rat displays significant NOS activity which can be dose-dependently inhibited by an NOS inhibitor. All three NOS isoform mRNA transcripts were present in the hypothalamus, with the order of expression being b-NOS > e-NOS > m-NOS. Immunohistochemical localization using monoclonal antibodies to the specific NOS isoform proteins revealed that b-NOS represented the major form of NOS in the hypothalamus based on density and distribution of immunostaining. b-NOS immunostaining was especially dense in the organum vasculosum laminae terminalis (OVLT), medial preoptic area (MPOA), supraoptic nucleus, and moderately dense in the arcuate nucleus/median eminence. The pattern and density of b-NOS staining closely mirrored our previously reported pattern of NADPH-diaphorase staining in the hypothalamus, and a polyclonal antibody to b-NOS yielded a similar staining pattern as that observed for the monoclonal antibody. In contrast to the dense staining observed for b-NOS in the hypothalamus, we observed no specific staining for m-NOS in the hypothalamus. e-NOS immunostaining, on the other hand, was present in the hypothalamus, but to a much lesser extent than b-NOS. Light e-NOS staining was observed in the OVLT, MPOA, supraoptic nucleus and arcuate nucleus/median eminence. That NO can regulate guanylate cyclase as a potential mediator of its effects was demonstrated using SNP which dose-dependently elevated cGMP levels in the POA and MBH of random cycling rats and estrogen-primed ovariectomized rats. The effect of SNP was due to its NO donor ability as it was blocked by the NO scavenger molecule, hemoglobin. Interestingly, hemoglobin alone caused a 50-60% reduction in basal cGMP levels, suggesting that endogenously produced NO regulates basal guanylate cyclase activity. Taken as a whole, the present study demonstrates that b-NOS is the major NOS isoform in the hypothalamus and it also provides evidence that cGMP may be a mediator of NO effects in the female hypothalamus as evidenced by the potent ability of SNP to elevate cGMP levels in the POA and MBH.
...
PMID:Evidence that brain nitric oxide synthase is the major nitric oxide synthase isoform in the hypothalamus of the adult female rat and that nitric oxide potently regulates hypothalamic cGMP levels. 885 3

The freely diffusible messenger nitric oxide (NO), generated by NO synthase (NOS)-containing "nitroxergic" (NO-ergic) neurons, is unique among classical synaptic chemical transmitters because of its "non-specificity", molecular "NO-receptors" (e.g. guanylyl cyclase, iron complexes, nitrosylated proteins or DNA) in target cells, intracellular targeting, regulated biosynthesis, and growth factor/cytokine-dependence. In the nervous system, expression of NOS is particularly intriguing in central and peripheral autonomic pathways and their targets. Here, anatomical and functional links appear to exist between NOS, its associated catalytic NADPH-diaphorase enzyme activity (NOSaD) and fibroblast growth factor-2 (FGF-2), a pleiotropic cytokine with mitogenic actions, suggesting mutual "short- and long-term" actions. Several recent studies performed in the rat sympathoadrenal system, an anatomically and neurochemically well-defined autonomic pathway with target-specific functional units of sympathetic preganglionic neurons (SPNs) in the spinal cord, provide evidence for this hypothesis. The NO and cytokine signals may interact at the level of gene expression, transcription factors, post-transcriptional control or second messenger cross-talk. Thus, unique biological roles of FGF-2 and the NO system are likely to exist in neuroendocrine actions, vasomotory perfusion control as well as in neurotrophic actions in sympathetic innervation of the adrenal gland. In view of their anatomical co-existence, functional interplay and synchronizing effects on neuronal networks, multiple roles are suggested for both "short- and long-term" signalling molecules in neuroendocrine functions and integrated autonomic target organ control.
...
PMID:Nitric oxide and fibroblast growth factor in autonomic nervous system: short- and long-term messengers in autonomic pathway and target-organ control. 910

In this study we evaluated the role of nitric oxide (NO) on gallbladder motility in the normal prairie dog by 1) immunohistochemistry, 2) an enzymatic assay for NO synthase (NOS), and 3) an in vivo model to measure whole gallbladder tone and contractility. NOS was localized to gallbladder mucosal cells by NADPH-diaphorase and polyclonal antibodies to a constitutive brain NOS. Gallbladder mucosal homogenates demonstrated total NOS activity in the range of 578 +/- 115 pmol x mg protein(-1) x 30 min(-1). Blockade of NOS activity in vivo using N(omega)-nitro-L-arginine methyl ester resulted in an up to 80% increase in gallbladder tone from basal. A 40% increase in tone was seen with methylene blue, suggesting that tone was maintained by both NO activation of guanylate cyclase and possibly direct effects on Ca2+ channels. An exogenous nitrosothiol, S-nitroso-N-acetyl-cysteine, abolished cholecystokinin (CCK) octapeptide and bethanechol-stimulated gallbladder contraction. We conclude that the prairie dog gallbladder contains constitutive NOS and synthesizes NO, which is important for the maintenance of basal gallbladder tone and is an inhibitor of the contractile response of the gallbladder to agonists such as CCK and bethanechol.
...
PMID:Nitric oxide and gallbladder motility in prairie dogs. 914 7

Recognition of the role of nitric oxide in cell-to-cell communication has changed the concept of traditional neurotransmission. We have shown previously that N-methyl-D-aspartate receptors mediate dipsogenic responses and c-Fos expression induced by intracerebroventricular infusion of angiotensin II. Since these receptors are known to be linked to the nitric oxide-cyclic GMP pathway, the present study explores the contribution of this path to the behavioural and cellular effects of intracerebroventricular angiotensin II by using behavioural testing, NADPH-diaphorase histochemistry and immunocytochemical staining for the immediate-early gene, c-fos. N(G)-nitro-L-arginine methyl ester (125 and 250 microg, intracerebroventricular), an inhibitor of nitric oxide synthase, and Methylene Blue (100 microg), an inhibitor of guanylate cyclase activation, antagonized water intake induced by intracerebroventricular injection of 25 pmol angiotensin II. The effects of N(G)-nitro-L-arginine methyl ester were reversed by co-injection of L-arginine, the substrate for nitric oxide synthase. However, N(G)-nitro-L-arginine methyl ester did not alter the pattern of angiotensin II-induced c-fos expression in the organum vasculosum of the lamina terminalis, median preoptic nucleus, hypothalamic paraventricular nucleus and supraoptic nucleus. Double staining with NADPH-diaphorase histochemistry and c-Fos immunocytochemistry showed that neurons staining for both were localized to the anterior third ventricle. However, only 19-25% of the c-Fos-positive neurons expressed NADPH. There were also substantial numbers of neurons in which angiotensin II induced c-Fos that were NADPH-negative. Extensive co-distribution of NADPH-diaphorase-stained cells and those expressing c-fos in response to intracerebroventricular injection of angiotensin II, especially in the median preoptic nucleus, imply that nitric oxide might participate in the mechanism of angiotensin II-induced drinking behaviour. However, a low rate of co-localization of the two markers to individual cells suggests that angiotensin II stimulated the production of nitric oxide and c-Fos in different populations of neurons. Since our previous results showed that glutamate blockade, but not nitric oxide synthase inhibition, suppressed angiotensin II-induced c-Fos, the experiments reported here further suggest that nitric oxide release is not an essential requirement for the expression of c-fos elicited by angiotensin II. They also provide evidence that the dipsogenic and c-Fos responses to angiotensin II are dissociated at a cellular level.
...
PMID:Angiotensin II interacts with nitric oxide-cyclic GMP pathway in the central control of drinking behaviour: mapping with c-fos and NADPH-diaphorase. 920 Jul 37

The participation of nitric oxide and vasoactive intestinal peptide (VIP) in the neurogenic regulation of bovine cerebral arteries was investigated. Nitrergic nerve fibers and ganglion-like groups of neurons were revealed by NADPH-diaphorase staining in the adventitial layer of bovine cerebral arteries. NADPH diaphorase also was present in endothelial cells but not in the smooth muscle layer. Double immunolabeling for neuronal nitric oxide synthase and VIP indicated that both molecules co-localized in the same nerve fibers in these vessels. Transmural nerve stimulation (200 mA, 0.2 milliseconds, 1 to 8 Hz) of endothelium-denuded bovine cerebral artery rings precontracted with prostaglandin F2 alpha, produced tetrodotoxin-sensitive relaxations that were completely suppressed by NG-nitro-L-arginine methyl ester (L-NAME) and by the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline (ODQ), but were not affected by the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22,536), nor by VIP tachyphylaxis induced by pretreatment with 1 mumol/L VIP. Transmural nerve stimulation also elicited increases in intracellular cyclic GMP concentration, which were prevented by L-NAME, and small decreases in intracellular cyclic AMP concentration. Addition of VIP to bovine cerebral artery rings without endothelium produced a concentration-dependent relaxation that was partially inhibited by L-NAME, ODQ, and SQ 22,536. The effects of L-NAME and SQ 22,536 were additive. VIP induced a transient increase in intracellular cyclic GMP concentration, which was maximal 1 minute after VIP addition, when the highest relaxation rate was observed, and which was blocked by L-NAME. It is concluded that nitric oxide produced by perivascular neurons and nerve fibers fully accounts for the experimental neurogenic relaxation of bovine cerebral arteries and that VIP, which also is present in the same perivascular fibers, acts as a neuromodulator by activating neuronal nitric oxide synthase.
...
PMID:Neuronal nitric oxide synthase activation by vasoactive intestinal peptide in bovine cerebral arteries. 930 11

Although the nitric oxide/cGMP pathway has many important roles in biology, studies of this system in the mammalian cochlea have focused on the first enzyme in the pathway, nitric oxide synthase (NOS). However, characterization of the NO receptor, soluble guanylate cyclase (sGC), is crucial to determine the cells targeted by NO and to develop rational hypotheses of the function of this pathway in auditory processing. In this study we characterized guinea pig cochlear sGC by determining its enzymatic activity and cellular localization. In cytosolic fractions of auditory nerve, lateral wall tissues, and cochlear neuroepithelium, addition of NO donors resulted in three- to 15-fold increases in cGMP formation. NO-stimulated sGC activity was not detected in particulate fractions. We also localized cochlear sGC activity through immunocytochemical detection of NO-stimulated cGMP. sGC activity was detected in Hensen's and Deiters' cells of the organ of Corti, as well as in vascular pericytes surrounding small capillaries in the lateral wall tissues and sensory neuroepithelium. sGC activity was not observed in sensory cells. Using NADPH-diaphorase histochemistry, NOS was localized to pillar cells and nerve fibers underlying hair cells. These results indicate that the NO/cGMP pathway may influence diverse elements of the auditory system, including cochlear blood flow and supporting cell physiology.
...
PMID:Localization of soluble guanylate cyclase activity in the guinea pig cochlea suggests involvement in regulation of blood flow and supporting cell physiology. 931 1

Biochemical and physiological studies suggested that increases in the levels of cyclic GMP in insect antennal receptor cells play a role in olfactory adaptation. As inositol-trisphosphate-dependent Ca2+ influx appears to precede the increase in intracellular cyclic GMP levels, it was hypothesized that a Ca2+-dependent mechanism might stimulate the guanylyl cyclase. The present study used histochemical staining for NADPH diaphorase to examine whether antennal receptor neurones of male Manduca sexta could contain nitric oxide synthase. This Ca2+/calmodulin-dependent enzyme is a prerequisite for nitric-oxide-dependent stimulation of guanylyl cyclase and possesses NADPH diaphorase activity. It was found that a subpopulation of olfactory receptor neurones as well as mechano-, thermo- and hygroreceptors on the moth antenna are NADPH-diaphorase-positive. Staining was also seen in non-neuronal cells. In the developing antenna, the NADPH-diaphorase-dependent staining was first observed at pupal stage 13-14, at approximately the same time as the antennal receptor neurones became physiologically active. The number and location of stained receptor cells was highly variable, and significantly more pheromone-sensitive sensilla were NADPH-diaphorase-positive in pheromone-stimulated antennae. This suggests that the enzyme is transiently activated by pheromone rather than being continuously active.
...
PMID:NADPH diaphorase activity in the antennae of the hawkmoth Manduca sexta 931 76


<< Previous 1 2 3 4 5 6 7 Next >>

---