Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus.

We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Based on the level of chronic kidney disease-associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 12) and CKD-aP (mild, moderate, or severe pruritus; n = 11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas.

A case of fibrillary glomerulonephritis associated with thrombotic microangiopathy and anti-glomerular basement membrane antibody.

We present the first report of a case of fibrillary glomerulonephritis (FGN) associated with thrombotic microangiopathy (TMA) and anti-glomerular basement membrane antibody (anti-GBM antibody). A 54-year-old man was admitted to our hospital for high fever and anuria. On the first hospital day, we initiated hemodialysis for renal dysfunction.

Chronotropic effects of azelnidipine, a slow- and long-acting dihydropyridine-type calcium channel blocker, in anesthetized dogs: a comparison with amlodipine.

Azelnidipine, a dihydropyridine calcium channel blocker unlike other dihydropyridine calcium channel blockers, does not increase but slightly decreases heart rate (HR) in clinical settings. In the present study, the mechanism for the HR-lowering action characteristic of azelnidipine was investigated in anesthetized dogs. In the in situ perfused sinus node preparation, the negative chronotropic action of azelnidipine was almost 5 times more potent than that of amlodipine.

Mechanism for atrial tachyarrhythmia in chronic volume overload-induced dilated atria.

Unlabelled: Mechanism of chronic volume overload-induced AT.

Introduction: Atrial dilatation associated with chronic volume overload (CVO) plays an important role in the development of atrial fibrillation (AF). However, the underlying mechanisms are unknown.

Differences in alpha 1-adrenoceptor subtype-mediated vasoconstriction by tyramine and nerve stimulation in canine splenic artery.

This study was designed to clarify the alpha(1)-adrenoceptor subtypes mediating the vasoconstrictor response to tyramine in isolated and perfused canine splenic artery. It was shown that tyramine potentiated the nerve stimulation-induced second peaked vasoconstriction that was readily suppressed by prazosin treatment. A bolus injection of tyramine (0.

Neurogenic double-peaked vasoconstriction of human gastroepiploic artery is mediated by both alpha1- and alpha2-adrenoceptors.

1. The contribution of postjunctional P2X receptors and subtypes of alpha-adrenoceptors to vasoconstrictor responses following periarterial electrical nerve stimulation (PNS, 30 s trains of pulses at a frequency of 2, 4 or 8 Hz) was investigated in human gastroepiploic arteries. 2.

Modification of transmitter release from periarterial nerve terminals by dipyridamole in canine isolated splenic artery.

1. The aim of the present study was to determine the modulatory effects of dipyridamole on purinergic and adrenergic transmission in the canine isolated, perfused splenic artery. 2.

Molecular cloning and expression of HRLRRP, a novel heart-restricted leucine-rich repeat protein.

We isolated a novel leucine-rich repeat protein (LRRP) cDNA from E13 mouse embryos by the in silico approach. The cDNA encoded a protein of 274 amino acids having 7 leucine-rich repeat motifs at the center of the protein. An in vitro transcription/translation study showed that the cDNA coded for a peptide of approximately 31kDa.

Cellular mechanism of pituitary adenylate cyclase-activating polypeptide-induced atrial tachyarrhythmia in canine isolated arterially perfused right atria.

1. Pituitary adenylate cyclase-activating polypeptide (PACAP) induces atrial tachyarrhythmia (AT). However, the cellular mechanism responsible for this remains unclear.

Purinergic and adrenergic cotransmission in canine isolated and perfused gastroepiploic arteries.

1. The vasoconstrictor responses of canine gastroepiploic artery to periarterial electrical nerve stimulation (PNS; 30 s trains of pulses at a frequency of 2, 4 or 8 Hz) were observed in a frequency dependent manner. The PNS-induced vasoconstrictions were abolished by tetrodotoxin (1 micromol/L) and mostly depressed but not completely by guanethidine (10 micromol/L).

The preferential inhibitory effect of olmesartan, a new angiotensin II type 1 antagonist, on sympathetic nerve terminals in isolated canine splenic artery.

Effects of olmesartan (RNH-6270: (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy-4-(1-hydroxy-1-methylethyl)-2-propyl[4-[2-(tetrazol-5-yl)-phenyl]phenyl]methylimidazol-5-carboxylase, an active form of olmesartan medoxomil (CS-866)) was investigated in isolated, perfused canine splenic arterial preparations. Neither exogenous noradrenaline- nor ATP-induced vasoconstrictor responses were modified by treatment with the used concentrations of olmesartan (1-100 nM). A high concentration of 10 nM angiotensin II caused a potentiation of either noradrenaline- and ATP-induced constrictions, although 1 nM angiotensin II did not induce any potentiating effects for these responses.

Neuroeffector mechanisms involved in the regulation of dog splenic arterial tone.

It has been recognized that sympathetic neurons release several transmitters but mainly adenosine 5'-triphosphate (ATP), noradrenaline, and neuropeptide Y (NPY). Recently, we reported that periarterial nerve electrical stimulation (PNS) produced biphasic vasoconstrictions consisting of an initial transient, predominantly P2X-purinoceptor-mediated constriction followed by a prolonged, alpha(1)-adrenoceptor-mediated one in canine isolated splenic arteries. In this article, we tried to analyze the effects of several selective key drugs that influence the PNS-induced responses, and we functionally showed sympathetic transmitter releasing mechanisms by pharmacological analysis using purinergic, adrenergic, and NPYergic agonists and antagonists.

Effects of reserpine on nerve stimulation-induced constrictions in canine isolated splenic artery.

1. Our previous studies have demonstrated that peri-arterial electrical nerve stimulation (PNS) of the canine splenic artery induces a double-peaked vasoconstriction consisting of an initial transient, dominantly P2X purinoceptor-mediated constriction, followed by a prolonged, mainly alpha1-adrenoceptor-induced response. In the present study, we examined the effects of reserpine on PNS-induced double-peaked responses.

Interaction between neuropeptide Y Y1 receptors and alpha1B-adrenoceptors in the neurovascular junction of canine splenic arteries.

Previous study has demonstrated that periarterial electrical nerve stimulation (30-s trains of pulses at a frequency of 1 or 4 Hz) induces a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X-receptor-mediated constriction followed by a prolonged, mainly alpha(1)-adrenoceptor-mediated response in the isolated canine splenic artery. Treatment with 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione (BMY 7378, 0.

Angiotensin II receptor subtypes involved in the modulation of purinergic and adrenergic vasoconstrictions to periarterial electrical nerve stimulation in the canine splenic artery.

Previous experiments demonstrated that periarterial electrical nerve stimulation induced a double-peaked vasoconstriction consisting of an initial transient, predominantly P2X-purinoceptor-mediated, constriction followed by a prolonged, mainly alpha1-adrenoceptor-mediated, response in the canine splenic artery. Angiotensin II at a concentration of 0.1 nM did not affect the basal vascular tone and vasoconstrictions to exogenously administered noradrenaline (0.

Relationship between ligand binding and YIPP motif in the C-terminal region of human AT1 receptor.

The YIPP (tyrosine-isoleucine-proline-proline, amino acids 319-322) motif within the C-terminal part of the human AT(1) receptor is associated with angiotensin II (AII)-induced activation of the Jak-STAT pathway and phospholipase Cgamma1 phosphorylation. We report here that mutations of the YIPP motif strongly affect ligand-binding to the receptor. We analysed AT(1) receptors of the wild type (WT) and 11 mutants with a FLAG-epitope-tag within their C-terminal portion.

Adenosine infusion inhibits adenosine-induced cardiac actions but enhances acetylcholine-induced actions in isolated dog atria.

Using isolated, blood-perfused canine atrial preparations, adenosine was continuously administered at various infusion rates into the cannulated sinus node artery. Adenosine induced negative chrono- and inotropic effects in an infusion-rate related manner. The inotropic responses to the adenosine infusion apparently faded but the chronotropic responses did not.

Existence of alpha-adrenoceptor subtypes in isolated human gastroepiploic and omental arteries.

Establishing the existence of alpha-adrenoceptor subtypes in isolated human gastroepiploic and omental arteries was the goal of the present study. Functional vascular reactivity of selective alpha(1)- and alpha(2)-adrenoceptor agonists and antagonists was studied, using a cannula inserting technique. Intraluminal administration of norepinephrine (NE), phenylephrine (PE) or BHT-933 caused a vasoconstrictive response in a dose-related manner.

Autonomic control of the location and rate of the cardiac pacemaker in the sinoatrial fat pad of parasympathetically denervated dog hearts.

Introduction: Parasympathetic activity predominates over sympathetic activity not only with respect to heart rate but also with respect to the pacemaker location in the dog heart. After we removed the parasympathetic neural elements in the sinoatrial (SA) fat pad in the right atrium, we observed that cervical vagus stimulation did not decrease the atrial rate, but it did suppress the increase in rate evoked by sympathetic stimulation. We determined whether the pacemaker rate and location were affected by presynaptic or postsynaptic mechanisms.

Effects of L-765,314, a selective and potent alpha 1B-adrenoceptor antagonist, on periarterial nerve electrical stimulation-induced double-peaked constrictor responses in isolated dog splenic arteries.

The periarterial nerve electrical stimulation (PNS) at a frequency of 1 or 4 Hz (30-s trains of pulses) readily caused a double peaked vasoconstriction in the canine splenic artery. The treatment with 1 microM L-765,314, a selective and potent alpha1B-adrenoceptor antagonist, markedly inhibited the second peaked constriction, whereas it did not modify the vasoconstrictor responses to exogenous noradrenaline (0.03-1 nmol) and A61603 (1-30 pmol), a selective alpha1A-agonist.

Botulinum neurotoxin A blocks cholinergic ganglionic neurotransmission in the dog heart.

There is no data about whether botulinum neurotoxin inhibits the parasympathetic ganglionic neurotransmission in the heart, although botulinum toxin as a clinical drug inhibits the release of acetylcholine at the neuromuscular junction. Therefore, we investigated whether botulinum toxin (type A) injected into the sinoatrial (SA) fat pad inhibits decreases in heart rate induced by stimulation of the preganglionic parasympathetic nerves in the heart of the anesthetized dog. Stimulation of the parasympathetic nerves in the SA fat pad (SAP stimulation) prolonged the atrial interval but not the atrioventricular (AV) interval, and cervical vagus nerve stimulation (CV stimulation) prolonged both atrial and AV intervals.

Antagonistic interaction between BIIE 0246, a neuropeptide Y Y2-receptor antagonist, and omega-conotoxin GVIA, a Ca2+ channel antagonist, in presynaptic transmitter releases in dog splenic arteries.

Isolated dog splenic arteries were perfused with Krebs-Henseleit solution at 37 degrees C, using the cannula inserting method. Periarterial nerve electrical stimulation (10-V amplitude; 1-ms duration; 30-s trains of pulses; 1, 4 and 10 Hz) readily caused double peaked vasoconstrictions, i.e.

Heterogeneous distribution of beta-adrenoceptors and muscarinic receptors in the sinoatrial node and right atrium of the dog.

1. The pacemaker site is known to shift away from the sinoatrial (SA) node in response to autonomic stimuli. 2.

Different sensitivities to alpha1 adrenoceptor blockade on periarterial sympathetic nerve-induced constriction by low and high frequencies in canine isolated splenic arteries.

The periarterial nerve electrical stimulation at 4 and 10 Hz induced a monophasic vasoconstriction of the canine splenic artery in a pulse number-related manner (1-30 pulses). The responses at 4 Hz were not significantly affected by 0.1 microM prazosin, but abolished by 1 microM alpha, beta-methylene ATP.

Existence of functional alpha1A- and alpha1D- but no alpha1B-adrenoceptor subtypes in rat common carotid arteries.

Using the cannula inserting method, vasoconstrictor responses to alpha1-adrenoceptor agonists (noradrenaline [NA], phenylephrine [PE] and methoxamine [ME]) and effects of alpha1-adrenoceptor antagonists (WB4101, chloroethylclonidine [CEC] and BMY7378) were investigated in isolated and perfused rat common carotid arteries. The rank order of agonist potency and efficacy was NA = PE > ME. Either WB4101 or BYM7378 inhibited NA- and PE-induced constrictions in a dose-related manner.