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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nishimura, J. Kitamura, K. Yasutsune, T. Yasui, H. Hirano, K. Kawakami, N. Kanaide, H. |
| Description | Author Affiliation: Yasutsune T ( Division of Molecular Cardiology, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.) |
| Abstract | Using fura-2 fluorometry, the effects of FK506, an immunosuppressant, on changes in cytosolic Ca2+ concentrations ([Ca2+]i) and tension were investigated in porcine coronary arterial strips. The effects of FK506 on the activity of voltage-operated Ca2+ channels were examined by applying a whole cell patch clamp to the isolated smooth muscle cells of porcine coronary artery. FK506 inhibited the sustained increases in both [Ca2+]i and tension induced by 118 mM K+ depolarization and 100 nM U46619 in a concentration-dependent manner (1-30 microM). The extent of inhibition of the K+-induced contraction was greater than that of the U46619-induced contraction. The increases in [Ca2+]i and tension induced by histamine and endothelin- in the presence of extracellular Ca2+ were also inhibited by 10 microM FK506. FK506 (10 microM) had no effect on Ca2+ release induced by caffeine or by histamine in the Ca2+-free solution. FK506 (10 microM) had no effect on the [Ca2+]i-tension relationships of the contractions induced by cumulative increases of extracellular Ca2+ during K+ depolarization or stimulation with U46619. In the patch clamp experiments, FK506 (30 microM) partially inhibited the inward current induced by depolarization pulse from -80 mV to 0 mV. In conclusion, FK506 induces arterial relaxation by decreasing [Ca2+]i mainly due to the inhibition of the L-type Ca2+ channels, with no effect on the Ca2+ sensitivity of the contractile apparatus. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 126 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-02-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Calcium Channels Drug Effects Coronary Vessels Immunosuppressive Agents Pharmacology Muscle Relaxation Tacrolimus 15-Hydroxy-11 Alpha,9 Alpha-(epoxymethano)prosta-5,13-dienoic Acid Animals Caffeine Calcium Metabolism Central Nervous System Stimulants Physiology Electric Stimulation Endothelin-1 Histamine In Vitro Techniques Isotonic Solutions Membrane Potentials Muscle Contraction Muscle, Smooth, Vascular Cytology Potassium Swine Vasoconstrictor Agents Vasodilation Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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