Specific attenuation of the pressure-induced contraction of rat cerebral artery by herbimycin A.
In order to determine whether protein tyrosine kinase mechanisms are involved in pressure-induced contraction, we compared effects of three structurally unrelated tyrosine kinase inhibitors and orthovanadate, a tyrosine phosphatase inhibitor, on the pressure-induced contraction of the posterior cerebral artery isolated from rats. The change in vessel diameter was continuously measured with a width analyzer. Herbimycin A inhibited the pressure-induced contraction, while it only slightly inhibited contractions produced by potassium chloride or 9,11-dideoxy-11alpha,9alpha-epoxymethano prostaglandin F2alpha (U46619). Genistein inhibited not only the pressure-induced contraction but also the U46619-induced one. Tyrphostin 23 significantly attenuated contractions in response to three different stimuli, i.e., pressure, potassium chloride and U46619. Orthovanadate potentiated the pressure-induced contraction. These results suggest that herbimycin A is a specific and potent inhibitor of the pressure-induced contraction and that a protein tyrosine kinase mechanism may play an important role in the genesis of the pressure-induced contraction of the rat cerebral artery.
Masumoto
N
N
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Japan.
Nakayama
K
K
Oyabe
A
A
Uchino
M
M
Ishii
K
K
Obara
K
K
Tanabe
Y
Y
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D016227:Benzoquinones; D002396:Catechols / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D019833:Genistein; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011312:Pressure; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017828:Rifabutin / Q000031:analogs & derivatives; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D020032:Tyrphostins; D014638:Vanadates / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016227:Benzoquinones; D002396:Catechols; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D009570:Nitriles; D011450:Prostaglandin Endoperoxides, Synthetic; D011809:Quinones; D020032:Tyrphostins; D014662:Vasoconstrictor Agents; D017828:Rifabutin; D014638:Vanadates; D013928:Thromboxane A2; D011189:Potassium Chloride; C020754:herbimycin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C060641:tyrphostin A23