Increase in tone and intracellular Ca2+ in rabbit isolated ear artery by platelet-derived growth factor.
1. The effect of platelet-derived growth factor (PDGF-AB) on tone and intracellular Ca2+ ([Ca2+]i) was examined in rabbit isolated ear arteries. Arteries were mounted in a myograph and loaded with the Ca(2+)-sensitive fluorescent indicator, fura-2, for concurrent measurements of isometric force and [Ca2+]i. 2. PDGF-AB contracted rabbit ear artery in a concentration-dependent manner. PDGF-AB induced tone was associated with a rise in [Ca2+]i. In the presence of noradrenaline, PDGF-AB induced a similar rise in [Ca2+]i but contraction in response to PDGF-AB in the presence of noradrenaline was increased compared with PDGF-AB alone. 3. PDGF-AB-induced rise in [Ca2+]i and tone were abolished by removal of extracellular Ca2+ (with addition of BAPTA, a Ca2+ chelator), and by preincubation with a dihydropyridine calcium channel blocker, (-)-202,791. Bistyrphostin, a selective inhibitor of tyrosine kinases, also inhibited PDGF-AB-induced tone, but had no effect on noradrenaline- or potassium-induced tone. 4. PDGF-AB contracts rabbit ear artery by increasing Ca2+ entry through voltage-operated calcium channels. This effect involves activation of a tyrosine kinase.
Hughes
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AD
Department of Clinical Pharmacology, St. Mary's Hospital Medical School, Imperial College of Science Technology and Medicine, London.
D000818:Animals; D001158:Arteries / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004423:Ear; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011817:Rabbits
D010982:Platelet-Derived Growth Factor; D011505:Protein-Tyrosine Kinases; D002118:Calcium; D009638:Norepinephrine