Protein tyrosine kinase signaling in cold-stimulated contraction of
newborn lamb cerebral arteries.
Wagerle, L. Craig, Sang Joo Kim, and Pierantonio Russo.
Departments of Physiology and Surgery, Temple University School of
Medicine, St. Christopher's Hospital for Children, and Department of
Cardiothoracic Surgery, Medical College of Pennsylvania and Hahnemann
University, Philadelphia, Pennsylvania
APStracts 2:0357H, 1995.
We have 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. The present study evaluated the effect of select
inhibitors of PTK and protein tyrosine phosphatase (PTP) on the
temperature-dependent contractile behavior of isolated MCA from
newborn lambs using tissue bath technique. Reduction of tissue bath
temperature from 37 degrees C 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 while staurosporine, an inhibitor of protein
kinase C, was without effect. Sodium orthovanadate (50 [mu]M)
potentiated the cold-stimulated contraction, augmenting the slope of
the temperature-force relationship over two-fold. Two ser/thr
phosphatase inhibitors (okadaic acid and calyculin A) had no effect
on the temperature-force relationship. These results offer an
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.
Received 14 June 1995; accepted in final form 1 August 1995.
APS Manuscript Number H542-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.