Effect of platelet-derived growth factor on voltage-operated calcium channels in rabbit isolated ear artery cells.
1. Platelet derived growth factor (PDGF), AB and BB isoforms (100 pM) increased calcium channel currents measured by whole cell voltage clamp technique in single vascular smooth muscle cells isolated from rabbit ear arteries. 2. Tyrphostin-23 (100 microM) a selective inhibitor of protein tyrosine kinases, reduced calcium channel currents. Pre-incubation with tyrphostin-23 prevented PDGF-AB induced increase in calcium channel currents. However, in these same cells 10 nM (+)-202791, a dihydropyridine calcium channel agonist, did increase calcium channel currents. 3. Bistyrphostin (10 microM), a selective inhibitor of epidermal growth factor (EGF)-kinase also reduced calcium channel currents and inhibited PDGF-AB-induced increases in calcium channel currents. 4. Genistein (100 microM) a selective inhibitor of tyrosine kinases, structurally unrelated to the tryphostins, also inhibited calcium channel currents and pre-incubation with genistein prevented the PDGF-AB-induced rise in calcium channel currents. 5. These results indicate that PDGF increases calcium channel currents in vascular smooth muscle. This action of PDGF probably involves a tyrosine kinase.
Wijetunge
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Department of Clinical Pharmacology, St. Mary's Hospital Medical School, Imperial College of Science Technology & Medicine, London.
Hughes
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D000704:Analysis of Variance; D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology; D004423:Ear / Q000098:blood supply; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009539:Nicotinic Acids / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011817:Rabbits; D013237:Stereoisomerism; D020032:Tyrphostins
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D002396:Catechols; D004791:Enzyme Inhibitors; D007529:Isoflavones; D009539:Nicotinic Acids; D009570:Nitriles; D010069:Oxadiazoles; D010982:Platelet-Derived Growth Factor; D020032:Tyrphostins; C049834:PN 202-791; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C060641:tyrphostin A23