Universität zu Köln

Zavaritskaya, Olga, Lubomirov, Lubomir T., Altay, Serdar and Schubert, Rudolf (2017). Src tyrosine kinases contribute to serotonin-mediated contraction by regulating calcium-dependent pathways in rat skeletal muscle arteries. Pflugers Arch., 469 (5-6). S. 767 - 778. NEW YORK: SPRINGER. ISSN 1432-2013

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Abstract

The Src tyrosine kinase family contributes to the signalling mechanism mediating serotonin (5-hydroxytryptamine (5-HT))-induced vasoconstriction. These kinases were reported to influence the calcium sensitivity of the contractile apparatus. Whether Src kinases affect also the intracellular calcium concentration during constriction of intact arteries is unknown. Thus, we tested the hypothesis that constriction of arteries is associated with a Src kinase-dependent alteration of the intracellular calcium concentration. Contractility of gracilis arteries of Wistar rats was studied using isometric and isobaric myography. The intracellular calcium concentration was measured simultaneously with tension by FURA-2 fluorimetry. Inhibition of Src kinases with 10 mu M PP2, 30 mu M dasatinib and 100 mu M AZM 475271 resulted in a strong attenuation of 5-HT-induced contractions. Vessel incubation with 10 mu M PP3, an inactive analogue of PP2, had no effect. Removal of the endothelium did not alter vessel contractile responses to 5-HT nor the action of the Src-kinase inhibitor PP2. The PP2-mediated inhibition of 5-HT-induced contraction was associated with a reduced response of [Ca2+](i) to 5-HT. In particular, inhibition of Src kinases attenuates 5-HT-induced calcium influx as well as calcium release from intracellular stores. In contrast, the calcium sensitivity of the contractile apparatus and the filling state of the sarcoplasmic reticulum were not influenced by Src kinases during 5-HT-induced contractions. We conclude that Src kinase activation is a powerful mechanism to produce vasoconstriction of small skeletal muscle arteries of rats. This effect is endothelium-independent. The data further suggest that the action of c-Src kinases is associated with a change in the intracellular calcium concentration that involves Ca2+ entry and Ca2+ release pathways.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Zavaritskaya, Olga UNSPECIFIED UNSPECIFIED UNSPECIFIED Lubomirov, Lubomir T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Altay, Serdar UNSPECIFIED UNSPECIFIED UNSPECIFIED Schubert, Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-229296
DOI:	10.1007/s00424-017-1949-3
Journal or Publication Title:	Pflugers Arch.
Volume:	469
Number:	5-6
Page Range:	S. 767 - 778
Date:	2017
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-2013
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VASCULAR SMOOTH-MUSCLE; C-SRC; RHO-KINASE; MESENTERIC-ARTERY; 5-HT2A RECEPTOR; FAMILY KINASES; CHANNELS; INHIBITOR; CELLS; VASOCONSTRICTION Multiple languages Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22929