title: Specific inhibition of stretch-induced increase in L-type calcium channel currents by herbimycin A in canine basilar arterial myocytes.
abstract: The effects of protein-tyrosine kinase (PTK) and protein-tyrosine phosphatase (PTP) inhibitors on voltage-activated barium currents (I(Ba)) through L-type calcium channels increased by hypotonic solution were investigated in canine basilar arterial myocytes by the whole-cell patch-clamp technique. I(Ba) was elicited by depolarizing step from a holding potential of -80 to +10 mV and identified by using an L-type calcium channel agonist, Bay K 8644 (100 nM), and an L-type calcium channel blocker, nicardipine (1 microM). Hypotonic superfusate induced cell swelling and acted as a stretch stimulus, which reversibly increased peak I(Ba) amplitude at +10 mV. I(Ba) was also decreased by nicardipine (1 microM) under the hypotonic condition. PTK inhibitors such as herbimycin A (30 nM), genistein (10 microM), and lavendustin A (10 microM) decreased I(Ba) enhanced by hypotonic solution. Genistein also decreased I(Ba) in a concentration-dependent manner under the isotonic condition. The inactive genistein analogue daidzein (10 microM) had no effect on I(Ba) under either the isotonic or hypotonic condition. By contrast, herbimycin A did not decrease I(Ba) under the isotonic condition. Sodium orthovanadate (10 microM), a PTP inhibitor, increased I(Ba) under both conditions. The present results suggest that cell swelling by hypotonic solution increases the L-type calcium channel currents in canine basilar artery and that herbimycin-sensitive PTK activity is primarily involved in the enhancement of calcium channel currents.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka City, Shizuoka 422-8526, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Obara
authors.forename: T
authors.initials: T
authors.lastname: Sasase
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Tanabe
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001488:Basilar Artery / Q000166:cytology; D016227:Benzoquinones; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D019833:Genistein / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D007552:Isotonic Solutions / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology; D010812:Physical Stimulation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D014638:Vanadates / Q000494:pharmacology
chemical_list: D016227:Benzoquinones; D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; D007038:Hypotonic Solutions; D007529:Isoflavones; D007552:Isotonic Solutions; D047029:Lactams, Macrocyclic; D010636:Phenols; D011809:Quinones; D017828:Rifabutin; D001464:Barium; D014638:Vanadates; C062898:lavendustin A; C004742:daidzein; C020754:herbimycin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009529:Nicardipine; D019833:Genistein; D011505:Protein-Tyrosine Kinases