Modulation of baroreflex sensitivity by the state of protein tyrosine phosphorylation in the brainstem of the rat.
Evidence accumulated recently suggests that protein tyrosine phosphorylation may play an important role in regulating neuronal functions. In the present study, we investigated if the state of protein tyrosine phosphorylation in the brainstem regulates baroreflex sensitivity. Anti-phosphotyrosine immunoblots of brainstem tissue revealed that several phosphotyrosine-containing proteins were present in the brainstem and their level of tyrosine phosphorylation was decreased by treatment of the slices with the protein tyrosine kinase (PTK) inhibitor genistein, and increased by treatment with the protein tyrosine phosphatase (PTP) inhibitor pervanadate. In urethane-anaesthetized rats, we found that inhibiting PTK activity by topical application of genistein to the dorsal surface of the medulla reduced the phenylephrine-induced baroreflex bradycardiac response. Conversely, the baroreflex response was potentiated by activating endogenous PTK activity with insulin or by inhibiting PTP activity with pervanadate. Thus these results suggest that the state of cellular tyrosine phosphorylation within the dorsal medulla of the brainstem may regulate the baroreflex control of heart rate, thereby providing the first evidence for a role for protein tyrosine phosphorylation, a key process involved in diverse intracellular signalling pathways, in modulating baroreflex sensitivity.
Man
H Y
HY
Department of Pathology, Hospital for Sick Children, University of Toronto, Toronto, Canada.
Erclik
T
T
Becker
L E
LE
Wang
Y T
YT
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014638:Vanadates / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D019000:Phosphotyrosine; D014638:Vanadates; D001285:Atropine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases