Protein tyrosine kinase signaling in cold-stimulated contraction of newborn lamb cerebral arteries. 1996

L C Wagerle, and S J Kim, and P Russo
Department of Physiology, Temple University School of Medicine, Philadelphia 19140, USA.

We recently reported a contraction of middle cerebral artery (MCA) preparations isolated from newborn lambs in response to tissue cooling. However, the mechanism(s) by which cold stimulus modifies the contractile properties of MCA is not known. We hypothesize that cold stimulus-triggered contraction may be mediated by a signal transduction pathway associated with protein tyrosine kinase (PTK)-dependent machinery. In the present study the tissue bath technique was used to evaluate the effect of select inhibitors of PTK and protein tyrosine phosphatase (PTP) on the temperature-dependent contractile behavior of isolated MCA from new-born lambs. Reduction of tissue bath temperature from 37 to 21 degrees C stimulated contraction (55 +/- 3% of the response to 120 mM KCl). Two distinct inhibitors of PTK, genistein and tyrphostin 47, completely reversed the cold-stimulated contraction, whereas staurosporine, an inhibitor of protein kinase C, was without effect. Sodium orthovanadate (50 microM) potentiated the cold-stimulated contraction, augmenting the slope of the temperature-force relationship over twofold. Two Ser/Thr phosphatase inhibitors (okadaic acid and calyculin A) had no effect on the temperature-force relationship. These results offer experimental evidence to support a novel hypothesis where PTK/PTP-dependent signal transduction pathways may be preferably targeted by cold stimulus and thus provide a biochemical basis for cold-stimulated modification of cerebral vascular contractile properties.

UI MeSH Term Description Entries
D008297 Male Males
D010744 Phosphoric Monoester Hydrolases A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. Phosphatase,Phosphatases,Phosphohydrolase,Phosphohydrolases,Phosphomonoesterase,Phosphomonoesterases,Phosphoric Monoester Hydrolase,Hydrolase, Phosphoric Monoester,Hydrolases, Phosphoric Monoester,Monoester Hydrolase, Phosphoric
D011505 Protein-Tyrosine Kinases Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors. Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D002536 Cerebral Arteries The arterial blood vessels supplying the CEREBRUM. Arteries, Cerebral,Artery, Cerebral,Cerebral Artery
D003080 Cold Temperature An absence of warmth or heat or a temperature notably below an accustomed norm. Cold,Cold Temperatures,Temperature, Cold,Temperatures, Cold
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures
D014638 Vanadates Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects. Decavanadate,Metavanadate,Orthovanadate,Oxyvanadium,Vanadyl,Monovanadate,Sodium Vanadate,Vanadate,Vanadate, Sodium

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