Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q96S42 (nodal)
 22,877 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship of the mononuclear cell (MNC) from human intestinal mucosa and mesenteric lymph node mediating anti-K-562 activity with that of peripheral blood has been assessed. Depletion of macrophages did not alter the measured cytotoxicity confirming that the effector cells were lymphocytes. Complement lysis of Leu 7 and Leu 11b coated cells reduced intestinal natural killer (NK) activity by a similar degree to that of peripheral blood but mesenteric lymph node NK activity was affected to a lesser extent. The response in NK activity of mucosal and nodal MNC to short incubation with lymphoblastoid interferon was similar to that for peripheral blood MNC. Twenty-four hours incubation of MNC with low concentrations of purified interleukin-2 (IL-2) consistently augmented intestinal and nodal NK activity but failed to augment that of peripheral blood MNC. No differences between the inhibitory effects of cAMP and prostaglandin E2 on NK activity from the three sites were seen. In addition, inhibition of cyclo-oxygenase activity with indomethacin had no effect on NK activity of intestinal and peripheral blood MNC while the lipoxygenase inhibitor, nordihydroguaiaretic acid, suppressed intestinal and peripheral blood NK activity similarly. In conclusion, anti-K-562 activity by intestinal MNC is mediated by NK cells with similar phenotypic and functional properties to those of peripheral blood. However, the increased sensitivity of mucosal NK cells to IL-2 suggests that higher proportions of NK cell precursors may be present in intestinal MNC populations.
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PMID:The nature of the natural killer (NK) cell of human intestinal mucosa and mesenteric lymph node. 241 37

Electrophysiological investigations of histamine in different cardiac tissues have led to the following results: Histamine and the H2-agonists dimaprit and impromidine show similar actions on electrophysiological parameters of ventricular myocardium (especially a decrease in action potential duration), which are completely blocked by cimetidine and enhanced by the phosphodiesterase inhibitor 1-methyl,3-isobutylxanthine (IBMX). These effects may be explained by an increase in cellular cAMP leading to an increase in slow inward current and outward currents as shown by voltage clamp experiments. Histamine in contrast to IBMX increases action potential duration at 90% repolarization (APD90) in atria. Histamine effects in atrial myocardium are completely reversed by the H1-antagonist dimetindene. Stimulation of atrial H1-receptors is suggested to directly cause an increase in Ca-channel conductance independent of intracellular cAMP content. Histamine reduces AH-interval, increases V max of NH-cells and may induce AV-node arrhythmias (at concentrations greater than or equal to 3 mumol/l). These effects remain unchanged by dimetindene, but are reversed by cimetidine. The results indicate that histamine increases AV-nodal conduction via H2-receptors. Unspecific membrane actions of cimetidine are not observed up to 100 mumol/l. Dimetindene increases action potential duration (APD) in left atria and decreases Vmax at concentrations greater than or equal to 10 mumol/l. However, H1-antagonistic actions of dimetindene are already observed at concentrations 1,000 to 10,000 times lower (pA2-values 8.39-9.12) so that unspecific membrane actions are suggested not to occur on a therapeutic dose level.
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PMID:Electrophysiological actions of histamine and H1-, H2-receptor antagonists in cardiac tissue. 242 81

The level of thyrostimulating autoantibodies (TSA) in IgG fraction isolated from the blood serum by precipitation of (NH4)2SO4 was determined in 36 patients with diffuse toxic goiter (DTG) and in 8 healthy donors. TCA which were assessed by a rise of the level of cAMP in human thyroid sections (obtained at operation from extranodal tissue of patients with nodal euthyroid goiter) after 2 h-incubation at 37 degrees C with IgG, were determined in 32 DTG patients (89%). The patients were divided into 2 groups with respect to their clinical and thyroid status: with a high and normal or subnormal content of the blood thyroid hormones. In the 1st group the frequency of detection (96%) and the level of TSA (570.64 +/- 109.63%) were much higher than in the 2nd group of patients (70 and 186.29 +/- 23.06%, respectively). The highest levels of TSA (1085.25 +/- 551.27%) were found in 4 of 26 patients (the 1st group) who had not received specific therapy.
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PMID:[Thyroid-stimulating autoantibodies in the blood of patients with diffuse toxic goiter]. 343 61

Ventricular and atrioventricular nodal cells from guinea pig and rabbit hearts were isolated by perfusing the heart with collagenase (Langendorff perfusion). In these cells the cyclic nucleotides cAMP and cGMP or Ca and EGTA were injected through a microelectrode by pressure (0.5-3 kg/cm2). The effect of injection on both the action potential and the hyperpolarization induced by acetylcholine was studied. The following results were obtained. 1. cAMP prolonged the ventricular action potential and shifted the plateau to more positive potentials. The configuration of the A-V nodal action potential was not detectably changed by cAMP injection, but the spontaneous rate was increased. 2. cGMP first shortened the ventricular action potential. In most experiments this effect was followed by long lasting prolongation of the action potential. 3. Both extracellular and intracellular application of dibutyryl cGMP shortened the ventricular action potential but did not produce a subsequent prolongation. However, prolongation was observed on injection of GMP, the direct metabolite. 4. Injection of cGMP in nodal cells did not hyperpolarize the membrane nor slow the spontaneous rate; rather, an increase in rate was observed. 5. The acetylcholine-induced hyperpolarization was not altered in amplitude or time course by the injection of cAMP, cGMP, Ca or EGTA. 6. The results support the hypothesis that cGMP might be involved in the control of voltage-controlled ionic channels but suggest that it does not play a role as a mediator of the classical muscarinic action i.e. the activation of a specific potassium channel by acetylcholine.
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PMID:The effect of intracellular cyclic nucleotides and calcium on the action potential and acetylcholine response of isolated cardiac cells. 628 Jan 26

We studied the effects of cholinergic agonists on slow delayed-rectifier K+ current (IKs) in isolated cells from the sino-atrial node (SAN) region of guinea pig heart, using patch-clamp procedures. Carbachol (5 nM to 10 microM) inhibited IKs in guinea pig SAN cells in the absence of previous beta-adrenergic stimulation and in cells pretreated with 8-(4-chlorophenylthio)-cAMP. Neither the muscarinic antagonist atropine nor the nicotinic antagonist hexamethonium antagonized carbachol inhibition of the current. Similar results were obtained with other cholinergic agonists. Cholinergic stimulation of the muscarinic K+ current was successfully antagonized by atropine in SAN cells where inhibition of IKs persisted. Therefore, the lack of antagonist effects on inhibition of IKs cannot be attributed to either an absence of muscarinic cholinoceptors on SAN cells or a loss of antagonist activity under our experimental conditions. These data demonstrate that cholinergic agonists, including the endogenous neurotransmitter acetylcholine, decrease the amplitude of IKs in guinea pig SAN cells via a non-muscarinic, non-nicotinic, cAMP-independent mechanism. Although the precise nature of this signal transduction pathway has not been elucidated, it is clearly different from those described for regulation of other nodal currents. Differential regulation of IKs in guinea pig SAN and ventricle cannot be attributed to higher basal adenylate cyclase activity in SAN cells. The inhibitory effect of carbachol on IKs was not additive with that of verapamil, a drug that is both an allosteric muscarinic antagonist and a potassium channel-blocking agent. Cholinergic agonists may inhibit IKs in SAN cells via a direct interaction with the SAN IKs channel.
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PMID:Cholinergic inhibition of slow delayed-rectifier K+ current in guinea pig sino-atrial node is not mediated by muscarinic receptors. 760 67

To characterize differences in regional cAMP production in the cardiac conduction system, 18 rats were anesthetized with pentobarbital (65 mg/kg IP) and randomized into a control (n = 9) and a stimulated group (n = 9). The stimulated group received aminophylline (20 mg/kg SC) and isoproterenol (16 micrograms/kg SC). The concentration of cAMP in freeze-dried, micro dissected pieces (1-3 micrograms) of cardiac tissue was measured using a new microanalytical method. The cAMP contents in right atrium, atrioventricular node, His bundle, and left ventricle (fmol/microgram dry weight, mean +/- SE) were 38.9 +/- 2.5, 39.0 +/- 4.3, 46.4 +/- 6.1, and 41.4 +/- 3.3 in controls and 72.9 +/- 6.7, 86.1 +/- 2.9, 115.0 +/- 11.5, and 79.5 +/- 7.3 in the stimulated group, respectively. Basal cAMP levels were similar throughout the heart, whereas isoproterenol increased cAMP levels in all regions (p < 0.01). Furthermore, cAMP levels in His bundle, after isoproterenol, were higher than in any other region (p < 0.05). These results demonstrate that: (a) cAMP can be measured in discrete portions of the cardiac conduction system; (b) there are significant regional differences of beta-adrenergic control in the cardiac conduction system; and (c) cAMP production after beta-adrenergic stimulation was lower than expected in the AV nodal region, based on previously described beta-adrenoceptor density measurements.
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PMID:Measurement of cAMP in the cardiac conduction system of rats. 776 30

The purpose of this review is to examine the role of the extracellular A1-adenosine (Ado) receptor in modulating membrane potential and currents in cardiac cells. The cellular electrophysiological effects of adenosine are both cell type- and species-dependent. In supraventricular tissues (SA, AV node, and atrium) of all species studied, the "direct" cAMP-independent activation of the inwardly rectifying K+ current IKAdo seems to be the most important action of adenosine. This current is activated by both adenosine and acetylcholine and flows through K+ channels with unitary slope conductance of about 45 pS and an open time constant of 1.4 ms. The density of K(+)-ACh,Ado channels is much less in ventricular than in atrial myocytes, and thus adenosine has little or no effect on the ventricular action potential. In atrial myocytes adenosine has a small inhibitory effect on basal L-type calcium current (ICa,L), but no effect on T-type calcium current (ICa,T). In ventricular myocytes, adenosine does not inhibit ICa,L (except ferret), ICa,T, or the sodium inward current INa. Adenosine has recently been shown to activate IKATP in ventricular membrane patches, but the relevance of this finding remains to be defined. Irrespective of cell type and species, adenosine inhibits membrane currents that are stimulated by beta-adrenergic agonists and other agents known to stimulate the activity of the enzyme adenylyl cyclase. This indirect cAMP-dependent mechanism of action has been shown to be responsible for the inhibition by adenosine of isoproterenol-stimulated ICa,L, delayed rectifier K+ current (IK), chloride current (ICl), the transient inward current ITi, and the pacemaker current IF. The importance of the actions of adenosine on membrane currents in modulation of atrial, ventricular, sinoatrial, and atrioventricular nodal function are discussed. Likewise, the antiarrhythmic and proarrhythmic actions of adenosine are discussed and the clinical implications of these actions are noted.
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PMID:Ionic basis of the electrophysiological actions of adenosine on cardiomyocytes. 789 4

The anteroventral periventricular nucleus (AVPV) is a nodal point in neural circuits regulating secretion of gonadotropin and contains sexually dimorphic populations of hormonally regulated dopamine-, dynorphin-, and enkephalin-containing neurons. Because the tyrosine hydroxylase (TH), prodynorphin (PDYN), and proenkephalin (PENK) genes contain cAMP response elements that control their expression in their promoters, we used histochemical methods to determine whether ovarian steroids alter expression of the cAMP response element-binding protein (CREB) in the AVPV. Because the ability of CREB to activate transcription depends on phosphorylation at Ser133, we also evaluated the effects of acute steroid treatment on levels of phosphorylated CREB (pCREB) in AVPV neurons by using an antibody that differentiates between CREB and pCREB. Treatment of ovariectomized rats with estradiol treatments caused a significant induction in the number of pCREB-immunoreactive nuclei within 30 min that was maintained for at least 4 hr, but did not alter CREB immunostaining in the AVPV. Pretreatment with the estrogen antagonist Nafoxidine blocked this induction. In contrast, acute administration of progesterone to estrogen-primed animals suppressed and then increased pCREB staining in the ASVPV at 30 and 60 min, respectively; no significant differences between experimental and control animals were apparent by 2 hr after progesterone treatment. Double-labeling experiments showed that pCREB was colocalized with PDYN, PENK, or TH mRNA in the AVPV, suggesting that pCREB may mediate the effect of steroid hormones on gene expression in these neurons.
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PMID:Hormonal regulation of CREB phosphorylation in the anteroventral periventricular nucleus. 862 33

We examined the role of endogenous NO in the autonomic regulation of atrioventricular (AV) nodal function by studying spontaneous action potentials (SAPs) and L-type Ca2+ current (ICa-L) in isolated single AV nodal cells from adult rabbit hearts. Both the perforated and the membrane-ruptured patch-clamp techniques in the whole-cell configuration were used under conditions known to alter NO production. Three NO donors, 3-morpholinosydnonimine (SIN-1, 0.1 mmol/L), S-nitroso-acetylcysteine (0.1 mmol/L), and sodium nitroprusside (0.1 mmol/L), suppressed the beta-adrenergic agonist isoproterenol (ISO, 1 mumol/L)-stimulated increase in ICa-L. SIN-1 also decreased the frequency and amplitude of SAPs. In cells in which ICa-L had been previously attenuated by the muscarinic agonist carbamylcholine (CCh, 1 mumol/L), SIN-1 had no additive effect. CCh activated an acetylcholine-sensitive outward K+ current (IK(ACh)) in AV nodal cells, in addition to the ICa-L inhibition. Intracellular dialysis with the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA, 0.5 mmol/L) blocked CCh-induced, but not SIN-1-induced, ICa.L attenuation. However, intracellular dialysis with methylene blue (20 mumol/L), which inhibits NO-mediated activation of guanylyl cyclase and cGMP production, blocked the effects of both CCh and SIN-1 on ICa-L. In these cells, neither L-NMMA nor methylene blue affected the CCh-activated IK(ACh). Direct application of cGMP (10 mumol/L) via internal dialysis significantly inhibited ISO-stimulated ICa-L. In AV nodal cells internally perfused with either a nonhydrolyzable cAMP analogue, 8-Br-cAMP (0.5 mmol/L), or a high concentration of cAMP (0.5 mmol/L), CCh did not inhibit, ICa-L but still activated IK(ACh). CCh-induced ICa-L attenuation could be abolished or quickly reversed by the nonselective phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (20 mumol/L). However, CCh still significantly suppressed ISO-stimulated ICa-L after the cGMP-inhibited PDE isozyme (PDE3) had been selectively inhibited by milrinone (5 mumol/L). Immunohistochemical staining identified the presence of the endothelial constitutive NO synthase (ecNOS or NOS3) in both single AV nodal cells in vitro and in cryostat sections of AV nodal tissue in situ. These results demonstrate that endogenous NO is involved in the muscarinic cholinergic attenuation of ICa-L in AV nodal cell; the mechanism likely involves the cGMP-stimulated PDE.
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PMID:Nitric oxide synthase (NOS3)-mediated cholinergic modulation of Ca2+ current in adult rabbit atrioventricular nodal cells. 863 50

After more than 15 years since the "new" interpretation of the Purkinje fibre's pacemaker current was proposed, much progress has been made in the understanding of the basic functional principles of cardiac pacemaking. We now know that, in both the SA node and Purkinje fibres, the diastolic depolarization is generated by the interplay of several ionic components, the key process being represented by the turning-on of the hyperpolarization-activated i(f) current towards the end of the action potential repolarization phase. The properties of i(f) are well suited not only to generate, but also to mediate the control of cardiac rate by autonomic transmitters. This control is exerted through modulation of adenylate-cyclase and of cAMP, and allows a fine and rapid adjustment of heart rate to the changing needs of our normal day-life. Still, several problems remain to be clarified : for example, it is not clear how the degree of involvement of i(f) and other components changes in different areas of the nodal region, and whether this process is under control of the autonomic nervous system; more importantly, it is still unknown if the pacemaking mechanisms are similar in the newborn and in the adult, or if developmental changes in the way pacemaker activity is generated and modulated exist.
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PMID:Cardiac pacemaker: 15 years of "new" interpretation. 893 64


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