-
[show abstract]
[hide abstract]
ABSTRACT: Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 mol/l) on the Na+ current using whole cell voltage clamp (tip resistance = 0.5 , [Na]i ando = 10 mmol/l at 18C). Aprindine revealed tonic block (Kdrest = 37.7 mol/l, Kdi = 0.74 mol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 mol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% 3070 at 1.5 ms, 82%6% at 20 ms, 93%7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na+ current by 3 mmol/l tosylchloramide sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = –100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 mol/l aprindine showed smaller use-dependent block (14% 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% 13%; n = 4) or at pH 8.0 (90% 12%; n = 4).The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.
Archiv für Experimentelle Pathologie und Pharmakologie 08/1991; 344(3):331-336. · 2.65 Impact Factor
-
Ichiro Hisatome,
Tatsuo Kato,
Hiroyuki Miyakoda,
Toru Takami,
Takaaki Abe,
Yasushi Tanaka,
Hiromoto Kosaka,
Kazuhide Ogino,
Yasuo Mitani,
Akio Yoshida,
Hiroshi Kotake,
Chiaki Shigemasa,
Hiroto Mashiba, Ryoichi Sato,
Akira Takeda
[show abstract]
[hide abstract]
ABSTRACT: Renal handling of urate in the hypouricemic patient with increase in both urate clearance (Cur) and Cur/creatinine clearance (Ccr) and normal urinary excretion of urate was studied according to the pharmacological evaluation. In the present case there was no response of urate excretion to either pyrazinamide or probenecid. Both furosemide and prednisolone could not alter Cur and Cur/ Ccr. Administration of inosine could have increased Cur, which was greater than Ccr. These results suggest that the present case had the defect of both pre- and postsecretory reabsorption of urate, accompanied by the existence of drug-insensitive secretion of urate, which is different from hitherto known types of renal hypouricemia, i.e. a novel type of renal hypouricemia.
Nephron 08/1970; 64(3):447-451. · 13.26 Impact Factor
-
Yasunori Tanaka,
Ichiro Hisatome,
Norihito Sasaki,
Gias U Ahmmed,
Toru Yatsuhashi,
Yumi Yamanouchi,
Kazuhiko Uchida,
Toshihiro Hamada,
Shin-ichi Taniguchi,
Kazuhide Ogino,
Osamu Igawa,
Akio Yoshida,
Chiaki Shigemasa, Ryoichi Sato
[show abstract]
[hide abstract]
ABSTRACT: Tocainide blocked the Na current (INa) in ventricular myocytes in either a tonic or a phasic block manner, having a higher affinity for the inactivated state (Kdi = 18 μM) than for the rested state (Kdrest = 606 μM). The degree of phasic block was enhanced and the onset of phasic block was faster with an increase in pulse duration as well as at less-negative holding potential (HP). The recovery-time constant from the phasic block of INa induced by tocainide was independent of either the HP or the removal of fast inactivation. After removal of fast inactivation, tocainide showed the pulse-duration dependency of phasic block but not the voltage dependency. These results suggest that tocainide could bind to the inactivated-state receptor through the hydrophilic pathway and leave the receptor through the hydrophobic pathway, producing the tonic and phasic block of INa.
General Pharmacology: The Vascular System.
-
Akio Yoshida,
Norihito Sasaki,
Atsumi Mori,
Shinichi Taniguchi,
Yoshihiko Ueta,
Kimihiko Hattori,
Yasunori Tanaka,
Osamu Igawa,
Mariko Tsuboi,
Hideo Sugawa, Ryoichi Sato,
Ichiro Hisatome,
Chiaki Shigemasa,
Evelyn F. Grollman,
Shinji Kosugi
[show abstract]
[hide abstract]
ABSTRACT: The electrophysiological properties of the Na+/I− symporter (NIS) were examined in a cloned rat thyroid cell line (FRTL-5) using the whole-cell patch-clamp technique. When the holding potential was between -40 mV and -80 mV, 1 mM NaI and NaSCN induced an immediate inward current which was greater with SCN− than with I− The reversal potential for I− and SCN− induced membrane currents was +50 mV. This is close to the value of +55 mV calculated by the Nernst equation for Na+. These results are consistent with I− and SCN− translocation via the NIS that is energized by the electrochemical gradient of Na+ and coupled to the transport of two or more Na+. There was no change in the membrane current recording with C1O4− indicating that C1O4− was either not transported into the cell, or the translocation was electroneutral. C1O4− addition, however, did reverse the inward currents induced by I− or SCN−. These effects of I−, SCN− and C1O4− on membrane currents reflect endogenous NIS activity since the responses duplicated those seen in CHO cells transfected with NIS. There were additional currents elicited by SCN− in FRTL-5 cells under certain conditions. For example at holding potentials of 0 and +30 mV, 1 mM SCN− produced an increasingly greater outward current. This outward current was transient. In addition, when SCN− was washed off the cells a transient inward current was detected. Unlike SCN−, 1–-10 mM I− had no observable effect on the membrane current at holding potentials of 0 and +30 mV. The results indicate FRTL-5 cells may have a specific SCN− translocation system in addition to the SCN− translocation by the I-− porter. Differences demonstrated in current response may explain some of the complicated influx and efflux properties of I−, SCN− and C1O4− in thyroid cells.
Biochimica et Biophysica Acta (BBA) - Biomembranes.
-
[show abstract]
[hide abstract]
ABSTRACT: 1.1. Plasma norepinephrine (NE), epinephrine (E), renin activity (PRA), angiotensin II (ATII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured in 20 male and 15 female subjects during submaximal treadmill test.2.2. Exercise duration was not different between the two groups (male vs. female: 13.4 ± 0.8 min vs. 11.6 ± 0.7 min, ns). Female subjects had higher heart rate during exercise, while systolic blood pressure at peak exercise was higher in male subjects.3.3. Plasma NE, E, ANP, and ATII responses were comparable between male and female subjects, but PRA both at rest and during exercise and ALD at rest were significantly higher in male subjects.4.4. Cardiac responses to submaximal exercise were different between male and female subjects, but neurohormonal responses were comparable between the two groups except for the high PRA at rest and during exercise and high plasma ALD at rest in male subjects.
General Pharmacology: The Vascular System.
-
Akio Yoshida,
Ichiro Hisatome,
Takahiro Nawada,
Norihito Sasaki,
Shin-ichi Taniguchi,
Yasunori Tanaka,
Ichiro Manabe,
Gias U. Ahmmed, Ryoichi Sato,
Atsumi Mori,
Kimihiko Hattori,
Yoshihiko Ueta,
Yasuo Mitani,
Masashi Watanabe,
Osamu Igawa,
Yukihiro Fujimoto,
Chiaki Shigemasa
[show abstract]
[hide abstract]
ABSTRACT: We have reported that thyroid K+ channel is activated by extracellular application of the thyroid-stimulating hormone (TSH) using single channel recording method performed on cloned normal rat thyroid cell (FRTL-5) membrane. Treatment of dibutyryladenosine cyclic monophosphate (Bt2 cAMP) also activated the TSH-dependent K+ channel. These findings indicate that the thyroid K+ channel is activated through the TSH-adenosine cyclic monophosphate (cAMP)-protein kinase A system. We examined the effects of amitriptyline on TSH-guanosine triphosphate binding protein (G protein)-adenylate cyclase-cAMP-K+ channel system in the cloned normal rat thyroid cell line FRTL-5. Amitriptyline inhibited the cAMP production induced by TSH. Amitriptyline also inhibited the cAMP production induced by cholera toxin, indicating that amitriptyline inhibited the thyroid G protein. Amitriptyline had no effect on TSH-receptor binding and cAMP production by forskolin (adenylate cyclase stimulator). Amitriptyline inhibited the K+ channel activation by cAMP, indicating that the suppressing mechanism is not the inhibition of TSH receptor or G protein but the direct suppression of K+ channel. It was concluded that amitriptyline inhibited the thyroid G protein and K+ channel.
European Journal of Pharmacology.
