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 distribution of cyclic guanosine 3',5' monophosphate (cGMP) producing cells in various organs of the rat were studied immunocytochemically using antibodies raised against formaldehyde-fixed cGMP. Sodium nitroprusside (SNP), a direct activator of guanylate cyclase and vasodilator, was used to enhance cGMP levels. In order to reach all organs optimally, whole body perfusion was performed using a modified Krebs-Ringer buffer at 37 degrees C, aerated with 5% CO2/95% O2, also containing isobutyl methyl xanthine (IBMX); a phosphodiesterase inhibitor. After 15-min pre-perfusion, SNP was added to the perfusate, followed by fast fixation with ice-cold 4% paraformaldehyde-phosphate buffer. After vehicle perfusion, only the retina showed cGMP immunoreactivity in the photoreceptor and ganglion layer, while other organs lacked cGMP immunoreactivity. After 15-min perfusion with SNP (10 microM), enhanced cGMP immunostaining was seen in smooth muscles of the aorta, amacrine-like cells in the retina, glomeruli of the kidney cortex, blood vessels in the dura mater, as well as cells in the pineal and in the median eminence. The results indicate that the distribution and the reactivity of cGMP producing cells, situated outside the blood brain barrier, can be studied by immunocytochemistry after pharmacological manipulations of the intact tissue with a nitrovasodilator using whole body perfusion.
...
PMID:cGMP immunocytochemistry in aorta, kidney, retina and brain tissues of the rat after perfusion with nitroprusside. 255 68

Coronary artery strips of cattle hearts in vitro respond to transmural stimulation with two potent but distinctly different responses. A neurogenic constriction, attributable to the endogenous release of acetylcholine, is predominant under conditions of minimal and moderate tone. During a high degree of spontaneous tone, and in the presence of near maximal contractions induced by 5-hydroxytryptamine, the response to field stimulation is relaxation rather than constriction. This process was studied more clearly after blockade of the cholinergic effects with atropine. The relaxation response elicited by 5 Hz stimulation for 2 min consisted of two components, one occurring during stimulation and the other promptly after its cessation. The overall relaxation was sufficient to almost obliterate a spontaneous contraction or a near-maximal contraction to 5-hydroxytryptamine. The relaxation to transmural stimulation was unaltered by tetrodotoxin, adrenergic blockade, indomethacin or 5 days cold storage of tissue. Relaxation was elicitable even by a single pulse. With a few pulses, the maximal effect was achieved at 0.5 Hz. Repeated application of three pulses, in strips with spontaneous tone, led to substantial but transient relaxations, which simulated spontaneous rhythm. Removal of the endothelium was without effect on the relaxations, and they were unaltered by inhibition of guanylate cyclase. In the presence of elevated potassium (30 mM), contractions to 5-hydroxytryptamine and those generated spontaneously did not relax to field stimulation. Inhibition of Na+-K+-ATPase with ouabain (5 microM) partially antagonized both components of the relaxation response.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Nonneurogenic relaxation to field stimulation in coronary arteries. 278 16

The interactions of the nitrovasodilators, endothelium-dependent vasodilators, and atrial peptides with cGMP synthesis have proved to be useful and important leads to the functions of cGMP and signal transduction mechanisms. Although considerable progress has been made, many important questions remain to be answered. Nevertheless, the guanylate cyclase-cGMP system clearly represents an important second-messenger system that mediates the effects of numerous agents.
Cold Spring Harb Symp Quant Biol 1988
PMID:Effects of nitrovasodilators, endothelium-dependent vasodilators, and atrial peptides on cGMP. 290 95

The need for nonshivering heat production, a principal function of brown adipose tissue, is accentuated in neonates. Accordingly, brown fat in the rat exhibits a very pronounced process of morphological and functional maturation perinatally, reaches a peak in its differentiation and heat-generating capacity within 1-2 weeks after birth, and undergoes involutive changes later in life. The later process of dedifferentiation can be either prevented or reversed by exposing the animals to cold ambient temperature for a prolonged period of time (cold acclimatization). The regulation of both the tissue maturation processes and the superimposed acute heat production are hormone mediated. Thus, the hormone receptor system within the adipocyte membrane and the sequence of molecular events interconnecting the initial hormonal stimulus with its final intracellular effect(s) are of considerable importance. The brown adipocytes of developing rats possess adrenoreceptors that can be pharmacologically classified as beta 1 (linked to adenylate cyclase) and alpha 2 (possibly linked to guanylate cyclase), multiple forms of cyclic nucleotide dependent and independent protein kinases, a protein kinase inhibitor, and at least two distinct phosphoprotein phosphatases associated with three phosphoprotein phosphatase modulators. The characteristics and developmental alterations of these regulatory components were studied in considerable detail by our group during the past decade. The results uncovered several target systems for ontogenic modifications of hormonal responses. Strong support was obtained for the hypothesis that protein phosphorylation and dephosphorylation is a major molecular mechanism involved in the regulation of both the brown adipocyte function and its proliferative activity during ontogenic development.
...
PMID:Mechanisms of hormonal regulations in brown adipose tissue of developing rats. 614 37

This study was undertaken to examine the possible role of nitric oxide (NO) on brown adipose tissue (BAT) thermogenesis in rats. The chronic administration of N omega-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor) in drinking water given to rats decreased interscapular BAT (IBAT) weight as well as DNA content in a warm environment (25 +/- 1 degrees C; 2 and 4 weeks), and inhibited the cold-stimulated (5 +/- 1 degrees C; 2 weeks) increase in IBAT weight and DNA content. L-Arginine administration (4 weeks in a warm environment) increased the DNA content of IBAT. Chronic L-NAME administration (2 weeks in a warm environment) eliminated the NE-stimulated increase in in vivo oxygen consumption (VO2), caused hypothermia in acute cold exposure (0 degree C), and suppressed the NE-stimulated increase in in vitro IBAT VO2. In vitro incubation of native IBAT with L-NAME suppressed the basal and NE-stimulated increase in in vitro VO2. In vitro incubation of IBAT with methylene blue (soluble guanylate cyclase inhibitor and a scavenger of free NO) eliminated the NE-stimulated increase in in vitro IBAT VO2. These results suggest that the nitric oxide and NO-cGMP signaling systems are involved in the regulation of BAT cellularity and thermogenesis in rats.
...
PMID:Effects of acute and chronic inhibition of nitric oxide synthase on brown adipose tissue thermogenesis. 904 15

Tissues are often cold stored for physiological studies and for clinical transplantation. We report that cold storage induces a relaxation to reoxygenation after hypoxia (H/R) in de-endothelialized porcine coronary arteries. In fresh denuded arteries stimulated with U46619, H/R did not elicit relaxation. However, after overnight cold storage (4 degrees C), H/R elicited a transient relaxation with peak relaxation of 56 +/- 8% (n = 8), which was reproducible after 2 days of cold storage. The H/R relaxation was inhibited by methylene blue (10 microM) and LY83583 (10 microM), O2-hemoglobin (1 microM), or N(G)-methyl-L-arginine (0.2 mM), but neither N(G)-nitro-L-arginine (0.2 mM) nor cyclo-oxygenase inhibition was effective. Importantly, the H/R relaxation was attenuated by KCl (40 mM) or tetrabutylammonium chloride (5 mM), a non-selective inhibitor of K+ channels. Interestingly, authentic nitric oxide (NO)- or S-nitroso-N-acetylpenicillamine (SNAP)-induced relaxations were enhanced by cold storage in U46619 (0.1 microM) contractures. When tissues were contracted with KCl (40 mM), the enhancement in NO- or SNAP-induced relaxation by cold storage was markedly smaller than with U46619. Neither catalase (1,200 U/ml) nor 3-amino-triazole (50 mM), an inhibitor of catalase, affected the H/R relaxation. The duration of H/R relaxation also increased with the period of incubation at 37 degrees C in the organ bath. This was blocked by inhibition of NO synthesis or guanylate cyclase. Moreover, inhibition of protein synthesis with actinomycin D (0.1 microM) and cycloheximide (10 microM), or dexamethasone (1 microM), an inhibitor of NO synthase induction, blocked this increase in the duration of the H/R relaxation. The results suggest that in smooth muscle induction of NO pathway relaxation, which is in part mediated by K+ channels and inducible NO synthase, may be of importance to the understanding of ischemia/reperfusion responses in cold-stored arteries.
...
PMID:Cold storage induces an endothelium-independent relaxation to hypoxia/reoxygenation in porcine coronary arteries. 934 33

The aim of our studies was to investigate hormonal prevention of hepatic preservation damage by the atrial natriuretic peptide (ANP) and the mechanisms involved. Isolated perfusion of rat livers was performed in a nonrecirculating fashion. Twenty minutes of preischemic perfusion was performed with or without different concentrations of ANP, followed by 24-hour storage in cold University of Wisconsin (UW) solution. Two hundred nanomoles of ANP prevented hepatocellular damage during a 2-hour reperfusion period as indicated by a marked attenuation of the sinusoidal efflux of lactate dehydrogenase (LDH) and purine nucleoside phosphorylase (PNP), and by reduced Trypan blue uptake. Furthermore, postischemic bile flow as an indicator of liver function was significantly improved by about 60% with 200 nmol/L ANP. No protection was conveyed by 20 nmol/L ANP nor by pretreatment with 200 nmol/L ANP for only 10 minutes. The effects of ANP seemed to be mediated by the guanylate cyclase-coupled A (GC-A) receptor and cyclic guanosine monophosphate (cGMP): whereas expression of both GC-A and GC-B receptors as well as of the GC-C receptor was found, cGMP did protect from ischemia-reperfusion damage, but selective ligands of the B and C receptor did not. To begin to determine the mechanisms of ANP-mediated protection, different parameters were investigated: ANP had no effect on portal pressure as an indicator of hepatic circulation, nor on intracellular energy depletion determined by adenosine nucleotide concentration. However, the marked augmentation of nuclear factor kappaB (NF-kappaB) binding activity during reperfusion was prevented in ANP-pretreated livers. In conclusion, pretreatment with ANP protects the rat liver from cold ischemia-reperfusion damage. This effect is mediated via the GC-A receptor and cGMP, and may be linked to an influence of ANP on NF-kappaB activation. Thus, ANP signaling via the GC-A receptor should be considered as a new pharmacological target to prevent preservation injury of the liver.
...
PMID:The guanylate cyclase-coupled natriuretic peptide receptor: a new target for prevention of cold ischemia-reperfusion damage of the rat liver. 979 16

This experiment was designed to determine mechanisms of change in nonadrenergic, noncholinergic (NANC) inhibitory neurons in the ileum after small bowel transplantation (SBT) in the rat and whether nitric oxide (NO) serves as an important NANC inhibitory neurotransmitter in the rat ileum. Eight groups of rats (N > or =8 rats/group) were studied: neurally intact unoperated controls; rats one week after anesthesia and sham celiotomy; and separate groups one and eight weeks after either 40 min of cold ischemia of the jejunoileum, combined jejunal and ileal intestinal transection/reanastomosis, or orthotopic SBT of the entire jejunoileum. Contractile activity was evaluated in full-thickness ileal circular muscle strips under isometric conditions. Spontaneous activity did not differ among groups. In all groups, exogenous NO, NG-monomethyl-L-arginine (L-NMMA, an NO synthase inhibitor), and methylene blue (soluble guanylate cyclase inhibitor) had no effect on spontaneous activity, while 8-bromocyclic guanosine monophosphate (8Br-cGMP) inhibited contractile activity in all groups. Low frequency (2-10 Hz) electrical field stimulation (EFS) inhibited contractile activity only in control and SBT groups; L-NMMA and methylene blue did not alter the response to EFS in any group. These results suggest that each aspect of the SBT procedure, ischemia/reperfusion injury, disruption of enteric neural continuity by intestinal transection, and extrinsic denervation, alter function of enteric ileal inhibitory neurons separately early (one week) after operation. NO, a known inhibitory neurotransmitter in other gut regions, does not affect ileal circular muscle in neurally intact tissue nor mediate functional changes in inhibitory nerve function nor smooth muscle contractility after SBT.
...
PMID:Functional changes in nonadrenergic, noncholinergic inhibitory neurons in ileal circular smooth muscle after small bowel transplantation in rats. 982 32

To elucidate the role of atrial natriuretic peptides (NPs) in the amphibian heart, the myotropic effects and the cardiac distribution of frog atrial natriuretic factor (fANF) have been studied in Rana esculenta. Spontaneously, beating in vitro isolated working heart preparations were treated with increased concentrations (10(-11)-10(-8) M) of fANF-(1-24). The peptide at 10(-9) and 10(-8) M significantly reduced heart rate (HR) and, on the electrically paced preparations, decreased cardiac output (CO), stroke volume (SV) and work. Such negative inotropism was abolished by pretreatment with the pertussis toxin or by blocking the particulate guanylate cyclase (GC) with anantin while it was independent both from the functional impairment of the endocardium-endothelium by Triton X-100 and the inhibition of the soluble guanylate cyclase by 1 H-(1,2,4,) oxadiazolo-(4,3-a) quinoxalin-1-one (ODQ). By autoradiography, two classes of high and low affinity NPs binding sites were detected in the ventricular endocardium and myocardium and in the bulbus arteriosus. The analysis of displacement binding data using the radioligand [125I]-rat atrial natriuretic peptide [125I-rANP-(1-28)], its cold counterpart and the fANF-(1-24) showed that in the ventricular myocardium, the low affinity NPs sites bound both the heterologous and the homologous ligands at a concentration close to that responsible for the negative inotropism and chronotropism.
...
PMID:Cardiac role of frog ANF: negative inotropism and binding sites in Rana esculenta. 1283 96

The role of nitric oxide (NO) in cardio-vascular homeostasis is now known to include allosteric redox modulation of cell respiration. An interesting animal for the study of this wide-ranging influence of NO is the cold-adapted Antarctic icefish Chionodraco hamatus, which is characterised by evolutionary loss of hemoglobin and multiple cardio-circulatory and subcellular compensations for efficient oxygen delivery. Using an isolated, perfused working heart preparation of C. hamatus, we show that both endogenous (L-arginine) and exogenous (SIN-1 in presence of SOD) NO-donors as well as the guanylate cyclase (GC) donor 8Br-cGMP elicit positive inotropism, while both nitric oxide synthase (NOS) and sGC inhibitors, i.e. L-NIO and ODQ, respectively, induce significant negative inotropic effects. These results therefore demonstrate that under basal working conditions the icefish heart is under the tonic influence of a NO-cGMP-mediated positive inotropism. We also show that the working heart, which has intracardiac NOS (shown by NADPH-diaphorase activity and immunolocalization), can produce and release NO, as measured by nitrite appearance in the cardiac effluent. These results indicate the presence of a functional NOS system in the icefish heart, possibly serving a paracrine/autocrine regulatory role.
...
PMID:No hemoglobin but NO: the icefish (Chionodraco hamatus) heart as a paradigm. 1547 16


1 2 3 Next >>

---