Ca Channel Blocker Nicardipine Research Articles

Anoctamin-like protein 1 regulates repolarization in Paramecium behavioral responses.

Paramecium exhibits responsive behavior to environmental changes, moving either closer to or further away from stimuli. Electrophysiological experiments have revealed that these behavioral responses are controlled by membrane potentials. Anoctamin, a Ca2+-activated Cl- channel, is involved in the regulation of membrane potential in mammals. However, it remains uncertain whether Cl- channels like anoctamin regulate Paramecium behavior. Herein, replacement of external Cl- ions with acetate ion and application of Cl- channel blocker niflumic acid (NFA, 0.1 μM) increased spontaneous avoiding reactions (sARs). Hence, we hypothesized that anoctamin is involved in the stabilization of membrane potential fluctuation. Paramecium cells in which the anoctamin-like protein 1 gene was knocked down displayed frequent sARs in the culture medium without external stimulation. Treatment of anoctamin-like protein 1-knockdown cells with the Ca2+ chelator BAPTA or Ca-channel blocker nicardipine reversed the increase in sARs. Electrophysiological experiments revealed extension of membrane depolarization when positive currents were applied to anoctamin-like protein 1-knockdown cells. We concluded that anoctamin-like protein 1 works as a Cl-channel and stabilizes the membrane potential oscillation, reducing sARs.

Insulin potentiating effect on development of alloxan diabetes and its prevention by the Ca-channel blocker nicardipine.

Insulin potentiating effect on development of alloxan diabetes and its prevention by the Ca-channel blocker nicardipine.

Effect of chemoradiotherapy using ACNU, vincristine, and nicardipine with high-dose irradiation on malignant astrocytomas.

Fifty-two patients with malignant astrocytoma were treated with cellular synchronization radiation therapy at the University of Tokyo Hospital between 1977 and 1989. Twenty-five patients (Group 1) received 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), vincristine, and 60 Gy of irradiation, and 27 patients (Group 2) ACNU, vincristine, the Ca-channel blocker nicardipine, and 72 Gy of irradiation. Median survival times for Groups 1 and 2 were 15 and 30 months, respectively. Although there was no significant difference, Group 2 achieved longer survival with 1-, 2-, and 3-year survival rates of 85.2, 65.8, and 46.9% compared to rates of 66.7, 40.0, and 26.7%, respectively, for Group 1.

Effects of endothelin on peptide-dependent cyclic adenosine monophosphate accumulation along the nephron segments of the rat.

We investigated the tubular action of endothelin in rat nephron segments. The effects of endothelin on arginine vasopressin (AVP)-, parathyroid hormone-, glucagon-, calcitonin-, and isoproterenol-dependent cAMP accumulation were studied. The following nephron segments were microdissected: glomerulus (Gl), proximal convoluted tubule (PCT), cortical and medullary thick ascending limbs of Henle's loop (cTAL and mTAL, respectively), cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and inner medullary collecting duct (IMCD). Endothelin dose dependently (10(-8)-10(-10)M) inhibited AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD. This effect was independent of the presence or absence of phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, Ca channel blocker nicardipine, or indomethacin, but was abolished in the presence of protein kinase C inhibitor H-7. Protein kinase C stimulator dioctanoyl glycerol mimicked the effect of endothelin. On the other hand, endothelin had no inhibitory effect on AVP-dependent cAMP accumulation in cTAL or mTAL, parathyroid hormone-dependent cAMP accumulation in Gl and PCT, or glucagon-, calcitonin-, and isoprotereol-dependent cAMP accumulation in OMCD. We conclude that endothelin specifically inhibits AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD through activating protein kinase C. This effect possibly has a role in maintaining urine volume to counteract the decrease in GFR caused by endothelin itself.

Inhibition of excitation-contraction coupling by a Ca channel blocker nicardipine at low temperature in frog twitch fibers.

Effects of a Ca channel blocker, nicardipine, on excitation-contraction (E-C) coupling were investigated in single twitch fibers dissected from short skeletal muscles of the frog, Rana japonica. The treatment with 20 microM nicardipine at 25 degrees C evoked a reversible twitch potentiation. By contrast, the treatment at the same concentration at 5 degrees C for 30 min evoked an intense twitch inhibition. The inhibition was irreversible. This paralyzed fiber remained at nearly normal resting and propagated action potentials. The treatment with 30 microM nicardipine for 14 min at 6 degrees C completely inhibited a potassium contracture by 190 mEq/l potassium ion for 1.5 h after the removal of nicardipine despite the retention of normal resting potentials. The paralyzed fiber which was previously treated with 20 microM nicardipine for 30 min at 6 degrees C, also remained at normal action potential and at partial potassium contracture, and responded to 3 mM caffeine stimulation with a normal contracture. Dose-dependence curves obtained from the data on the treatments with nicardipine at various concentrations for 30 min at 6 degrees C consisted of an opposite sigmoidal shape with both threshold and half maximum inhibition at 1 and 1.5 microM for twitch and similarly at 5 and 12 microM for potassium contracture. Temperature-dependence curves obtained from the data on the treatments with 20 microM nicardipine for 30 min at various temperatures consisted of a sigmoidal shape with half maximum inhibition at 15 degrees C for twitch and at 12 degrees C for potassium contracture. A working hypothesis "two component-three state model" for E-C coupling was proposed based on the interpreted mechanism of nicardipine action.