Microtubule disruption potentiates receptor-mediated vasoconstriction

A. Melis, D. G. Johns, J. L. Park, R Clinton Webb

Research output: Contribution to journalArticle

Abstract

Disruption of microtubules induces shortening in cultured cells and potentiates agonist-induced contraction in isolated pulmonary arteries from rats. Presumably, the cytoskeletal microtubules alter cell function in three ways: 1) they serve as rigid struts opposing cellular contraction; 2) microtubules enhance transduction of signals mediated by GTP-binding proteins; and 3) microtubules associate with protein kinases. In this study, we tested the hypothesis that microtubules oppose contraction induced by receptor activation and subsequent generation of second messengers in vascular smooth muscle. Helically-cut aortic strips (no endothelium) from normotensive rats (n=2-4) were placed in isolated organ baths for measurement of isometric force generation using standard muscle bath techniques The aortic segments were made to contract in response to serotonin (3 μM 5-HT) in physiologic buffer containing 1.6 mM Ca2+. After a depletion period in Ca2+-free medium, aortic segments were made to contract in response to 5-HT (receptor-mediated) or caffeine (20 mM, non-receptor-mediated). Disruption of microtubules by incubation with nocodazole, colchicine and vinblastine (10 μM) potentiated force development to 5-HT in Ca2+-free medium (41 to 140% increase in force development) but not force induced by caffeine. The increased contractile response to 5-HT in the presence of nocodazole was attenuated by the microtubular stabilizer, taxol (20 μM). This study demonstrates that disruption of microtubules increases vascular contraction to receptor activation implying that the microtubules enhance transduction of intracellular signals.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

Fingerprint

Vasoconstriction
Microtubules
Serotonin
Nocodazole
Caffeine
Muscle
Rats
Chemical activation
Vinblastine
Serotonin Receptors
Struts
Colchicine
Second Messenger Systems
Paclitaxel
Baths
GTP-Binding Proteins
Protein Kinases
Signal Transduction
Buffers
Cells

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Microtubule disruption potentiates receptor-mediated vasoconstriction. / Melis, A.; Johns, D. G.; Park, J. L.; Webb, R Clinton.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

Melis, A. ; Johns, D. G. ; Park, J. L. ; Webb, R Clinton. / Microtubule disruption potentiates receptor-mediated vasoconstriction. In: FASEB Journal. 1998 ; Vol. 12, No. 5.
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