Platelet-activating factor activates cardiac GK via arachidonic acid metabolites.

Platelet-activating factor (PAF), added to the bathing solution, stimulated the cardiac muscarinic K+ channel (KACh) in the cell-attached patch (no agonist in the pipette). The PAF-induced KACh channel activation was blocked by WEB2086, a PAF-receptor inhibitor, indicating that the PAF-receptor mediated the response. PAF-induced activation was prevented by nordihydroguaieretic acid, a lipoxygenase inhibitor, and AA-861, a 5-lipoxygenase inhibitor, but was not affected by indomethacin, a cyclo-oxygenase inhibitor.

On the mechanism of basal and agonist-induced activation of the G protein-gated muscarinic K+ channel in atrial myocytes of guinea pig heart.

Using the patch clamp technique, we examined the agonist-free, basal interaction between the muscarinic acetylcholine (m-ACh) receptor and the G protein (GK)-gated muscarinic K+ channel (IK.ACh), and the modification of this interaction by ACh binding to the receptor in single atrial myocytes of guinea pig heart. In the whole cell clamp mode, guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma S) gradually increased the IK.

Beta-angonists modulate ACh-inhibition of a K current in intestinal smooth muscle cells.

ACh causes a long-lasting inhibition of STOCs via G proteins in intestinal smooth muscle cells. We examined the effects of isoproterenol (Iso) on the ACh-induced inhibition of STOCs in isolated ileal smooth muscle cells using the G omega-seal whole cell clamp technique. In control, ACh (1 microM) completely suppressed STOCs, which did not desensitize over a period lasting 20 minutes.

Coenzyme Q10 attenuates cyanide-activation of the ATP-sensitive K+ channel current in single cardiac myocytes of the guinea-pig.

The effect of coenzyme Q10 (CoQ10) on the cyanide (CN-)-induced ATP-sensitive K+ channel current (KATP) was examined in single atrial myocytes, using the patch clamp technique. Superfusion of the cells with a CN-/low glucose bathing solution induced an outward current in the whole-cell clamp condition. Glibenclamide (1 microM) abolished this current, indicating that the current was carried through the KATP channel.

On the mechanism of nucleotide diphosphate activation of the ATP-sensitive K+ channel in ventricular cell of guinea-pig.

1. Effects of intracellular nucleotide diphosphates (NDPs) on the ATP-sensitive K+ channel (K+ATP channel) were examined in ventricular cells of guinea-pig heart, using the inside-out patch clamp technique. On formation of inside-out patches in the ATP-free internal solution, the K+ATP channel appeared and then ran down spontaneously.

Voltage-gated K+ channels in the mouse interleukin 3-dependent cell line, FDC-P2.

The electrical properties of a mouse interleukin (IL)-3-dependent cell line, FDC-P2, were examined using the tight-seal whole-cell clamp technique. Under current clamp conditions with 140 mM K+ in the pipette, the cells had a resting potential of approximately -30 mV. Under voltage-clamp conditions, a transient outward current was elicited upon depolarization from a holding potential of -80 mV.

Glibenclamide specifically blocks ATP-sensitive K+ channel current in atrial myocytes of guinea pig heart.

Effects of glibenclamide on the control membrane ionic currents, acetylcholine or adenosine-induced K+ current, and nicorandil-induced K+ current were examined in single atrial myocytes of guinea pig heart. The nystatin-whole cell clamp technique was used. Nicorandil evoked the time-independent K+ current which is probably the current through the ATP-sensitive K+ channel.

Adenosine-5'-triphosphate-induced sinus tachycardia mediated by prostaglandin synthesis via phospholipase C in the rabbit heart.

Effects of adenosine 5'-triphosphate (ATP) and adenosine on cardiac sinus pacemaker activity were examined in the rabbit heart. Electrocardiograms of hearts were recorded while using the Langendorff perfusion method. Both adenosine and ATP, added to the perfusate, slowed the sinus pacemaker activity in a concentration-dependent manner.

Heparin uncouples the muscarinic receptors from GK protein in the atrial cell membrane of the guinea-pig heart.

The effects of heparin on activation of the G protein-gated muscarinic K+ channel were examined in atrial cells of guinea-pig heart. The inside-out patch clamp technique was used. The pipette solution contained 1.

Purification and characterization of five different alpha subunits of guanine-nucleotide-binding proteins in bovine brain membranes. Their physiological properties concerning the activities of adenylate cyclase and atrial muscarinic K+ channels.

We have purified five different alpha subunits of guanine-nucleotide-binding proteins (G proteins) from bovine brain membranes as active forms bound to guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]). All the purified alpha subunits were interacted with beta gamma subunits and served as a substrate for pertussin-catalyzed ADP-ribosylation. Based on the findings of immunoblot analyses using specific antibodies raised against various alpha subunits of G proteins, three of them were identified as alpha i-1, alpha i-2 and alpha i-3, and the other two were classified into alpha o type.

Positive cooperativity in activation of the cardiac muscarinic K+ channel by intracellular GTP.

Concentration-dependent effects of intracellular GTP on activation of the muscarinic K+ channel were examined in inside-out patches of cardiac atrial myocytes. The pipette solution contained 0.1 microM ACh.

Properties of membrane currents in isolated smooth muscle cells from guinea-pig trachea.

Tracheal smooth muscle cells were enzymatically isolated from guinea-pig trachea. These cells contracted in response to acetylcholine (0.01-10 microM) in a concentration-dependent fashion.

Trimebutine maleate has inhibitory effects on the voltage-dependent Ca2+ inward current and other membrane currents in intestinal smooth muscle cells.

We examined effects of trimebutine maleate on the membrane currents of the intestinal smooth muscle cells by using the tight-seal whole cell clamp technique. Trimebutine suppressed the Ba2+ inward current through voltage-dependent Ca2+ channels in a dose-dependent manner. The inhibitory effect of trimebutine on the Ba2+ inward current was not use-dependent.

Voltage-dependent inhibition of the delayed outward potassium current by OPC-8490, a novel positive inotropic agent, in isolated atrial myocytes of guinea-pig heart.

To elucidate the ionic mechanisms underlying prolongation of the action potential by OPC-8490, a novel positive inotropic agent, we examined effects of the drug on the membrane currents in isolated atrial myocytes of guinea-pig heart. The tight-seal whole cell clamp technique was used. In the current clamp condition, OPC-8490 prolonged the atrial action potential in a concentration-dependent fashion.

Biosynthesis and functions of leukotriene C4.

1. The LTC4 synthase activity is rich in the microsomal fraction of the guinea pig spleen and lung. The enzyme was partially purified from the guinea pig lung and separated from the microsomal glutathione S-transferase (GST), by column chromatograpy.

Cheilitis glandularis: report of a case affecting the upper lip.

Cheilitis glandularis is a rare disorder characterized by swelling of the lip with hyperplasia of labial salivary glands, typically in the lower lip of adult males. A definitive cause and treatment for this disorder have not yet been established. Herein is reported a case of cheilitis glandularis affecting the upper lip with nodules, treated by surgical excision with good post-surgical results.

Effect of adenosine and adenosine analogs on [14C]aminopyrine accumulation by rabbit parietal cells.

Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on [14C]aminopyrine accumulation by rabbit parietal cells.

Cardiac Ca current does not run down and is very sensitive to isoprenaline in the nystatin-method of whole cell recording.

The conventional L type Ca2+ channel current (ICa.L) was measured in single atrial and ventricular myocytes, with a new whole-cell recording technique using an ionophore, nystatin. The membrane of a cell-attached patch was gradually permeabilized by nystatin (100-200 micrograms/ml), added to the pipette solution, within 2-5 min after formation of a G omega-seal.

AN-132, a new class I anti-arrhythmic agent, depresses the acetylcholine-induced K+ current in atrial myocytes.

AN-132, a newly developed anti-arrhythmic agent, effectively depressed the acetylcholine (ACh)-induced K+ current (IK.ACh), as measured with the tight-seal, whole-cell clamp technique in single atrial cells of guinea-pig. When GTP-gamma S was loaded into the cell through a pipette, IK.

Alpha-adrenergic activation of the muscarinic K+ channel is mediated by arachidonic acid metabolites.

Phenylephrine (10 microM), added in the bathing solution, stimulated the cardiac muscarinic K+ channel (IK.ACh) in the cell-attached patch. The pipette solution contained 10 microM atropine and 100 microM theophylline to block the muscarinic acetylcholine and adenosine receptors, respectively.

Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel.

Arachidonic acid is released from cell membranes in response to receptor-dependent as well as receptor-independent stimulation in various cells, including cardiac myocytes. Arachidonic acid is converted to prostaglandins by cyclooxygenase and to leukotrienes by 5-lipoxygenase, metabolites which are very biologically active and modulate cellular functions such as platelet aggregation, smooth muscle contraction and neural excitation. The molecular mechanisms underlying their modulations are, however, still badly understood.