title: Novel mechanism by which hemoglobin induces constriction of cerebral arteries.
abstract: Since oxyhemoglobin (OxyHb) is implicated in the pathogenesis of cerebral vasospasm, we have investigated the role of protein tyrosine phosphorylation in OxyHb-mediated signalling in canine cerebral arteries and cultured canine cerebrovascular smooth muscle cells. OxyHb produced a contraction of basilar artery preparations, which was reversed by genistein, an inhibitor of tyrosine kinases, and PD098059, an inhibitor of mitogen-activated protein kinase. In cerebrovascular smooth muscle cells, OxyHb induced tyrosine phosphorylation of 42, 46, 54-60 and 80-100 kDa proteins with a time-course which paralleled the contractile action of OxyHb, suggesting that these events might be functionally linked. The 42 and 60 kDa proteins were immunologically related to the mitogen-activated protein kinase, extracellular signal regulated protein kinase (ERK2), and to p60c-Src (c-Src), respectively. The increase in protein tyrosine phosphorylation was attenuated by genistein, and the phosphorylation of the 42 kDa protein (ERK2) was inhibited by PD098059. These results suggest that OxyHb-mediated signalling utilizes a protein tyrosine kinase-based mechanism.
authors.affiliation: Department of Pharmacology, University of Alberta, Edmonton, Canada. bozena.vollrath@ualberta.ca
authors.forename: B
authors.initials: B
authors.lastname: Vollrath
authors.forename: D
authors.initials: D
authors.lastname: Cook
authors.forename: J
authors.initials: J
authors.lastname: Megyesi
authors.forename: J M
authors.initials: JM
authors.lastname: Findlay
authors.forename: H
authors.initials: H
authors.lastname: Ohkuma
mesh_terms: D000818:Animals; D002536:Cerebral Arteries / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006454:Hemoglobins / Q000502:physiology*; D008297:Male; D010108:Oxyhemoglobins / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism; D014661:Vasoconstriction
chemical_list: D006454:Hemoglobins; D010108:Oxyhemoglobins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases