Item – Theses Canada

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OCLC number
46552458
Link(s) to full text
LAC copy
LAC copy
Author
Murdoch, Gordon Kenneth,1967-
Title
The modulation of cyclic nucleotides in rat pinealocytes by a tyrosine kinase inhibitor, tyrphostin B42.
Degree
M. Sc. -- University of Alberta, 1997
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [1998]
Description
2 microfiches.
Notes
Includes bibliographical references.
Abstract
In this study, the effects of a substrate-site acting tyrosine kinase inhibitor, tyrphostin, on the cyclic nucleotide accumulation in dispersed male rat pinealocytes were examined. Treatment with 300 $\mu$M tyrphostin B42 increased both the cAMP and cGMP accumulation above basal levels. The extent of tyrphostin B42-induced cyclic nucleotide accumulation increase was more substantial for cGMP than cAMP, suggesting tonic regulation of these nucleotides is different. Activation of the adrenergic linked cyclic nucleotide pathway using isoproterenol (1 $\mu$M), norepinephrine (10 $\mu$M) or forskolin (10 $\mu$M) elevated cAMP accumulation, which was further elevated in the presence of tyrphostin B42. The use of tyrphostin A1, a less potent tyrosine kinase inhibitor, demonstrated that the observed effects of tyrphostin B42 are likely associated with inhibition of tyrosine phosphorylation(s). The use of isobutylmethylxanthine (IBMX) (1 $\mu$M) to inhibit the phosphodiesterase activities revealed that this is one probable site of action of tyrphostin B42, and further, that tyrphostin B42 has a second site of action that results in a decreased cyclic nucleotide accumulation in adrenergically-stimulated and IBMX-treated pinealocytes. This study augments the growing data which demonstrate the involvement of tyrosine kinase activity in G-protein coupled signal transduction pathways.
ISBN
0612226441
9780612226449