عنوان

Ca(2+)-desensitization in smooth muscle:

Number

TLpq304461542

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Ca(2+)-desensitization in smooth muscle:

General Material Designation

[Thesis]

First Statement of Responsibility

X. Wu

Title Proper by Another Author

From cyclic nucleotides, telokin, to myosin light chain phosphatase

Subsequent Statement of Responsibility

A. V. Sombyo

Name of Publisher, Distributor, etc.

University of Virginia

Date of Publication, Distribution, etc.

1998

Specific Material Designation and Extent of Item

112

Dissertation or thesis details and type of degree

Ph.D.

Body granting the degree

University of Virginia

Text preceding or following the note

1998

Text of Note

Cyclic nucleotides, cAMP or cGMP, relaxes smooth muscle by lowering usd\rm\lbrack Ca\sp{2+}\rbrack\sb{in}usd and/or decrease the sensitivity of contractile elements to usd\rm Ca\sp{2+}.usd The following results suggested that enhancement of smooth muscle myosin light chain phosphatase (SMPP-1M) activity accounted for usd\rm Ca\sp{2+}usd-desensitization induced by cGMP: cGMP-dependent relaxation of smooth muscle was associated with a decrease in phosphorylation of the regulatory myosin light chain (MLC{20}); cGMP accelerated both relaxation and dephosphorylation of MLC{20} independently of myosin light chain kinase activity; cGMP did not affect thiophosphorylation of MLC{20}. Furthermore, 8-bromo-cGMP-dependent stimulation reversed G-protein-coupled inhibition of SMPP-1M activity. Incorporation of P into telokin, a smooth muscle-specific, 17-18 kDa, acidic protein, was increased by forskolin in intact and by 8-bromo-cGMP in usd\alphausd-toxin permeabilized rabbit ileum smooth muscle (ileum). Native telokin, purified from turkey gizzard, and recombinant rabbit telokin, expressed in E. coli and purified, induced dose-dependent relaxation, associated with a significant decrease in MLC{20} phosphorylation, without affecting the rate of thiophosphorylation of MLC{20} of ileum permeabilized with Triton X-100. It remains unclear whether telokin has a direct stimulatory effect on SMPP-1M. Endogenous telokin was lost from ileum during permeabilization with Triton X-100, and the time course of loss was correlated with the loss of 8-bromo-cGMP-induced Ca-desensitization. Recombinant and native telokins were phosphorylated, in vitro, by the catalytic subunit of cAMP-dependent protein kinase, cGMP-dependent protein kinase (PKG), p42/44 mitogen-activated protein kinase; the recombinant protein was also phosphorylated by calmodulin-dependent protein kinase II. Exogenous PKG activated by 8-bromo-cGMP phosphorylated recombinant telokin when added concurrently to ileum depleted of its endogenous telokin and their relaxant effects were mutually potentiated. Based on these findings, we propose that telokin induces Ca-desensitization in smooth muscle by enhancing SMPP-1M activity and cGMP- and/or cAMP-dependent phosphorylation of telokin upregulates its relaxant effect. More studies have been carried out to test this hypothesis, to determine the physiological role of telokin and how it is regulated.

Biological sciences

Calcium desensitization

Cyclic nucleotides

Myosin

Phosphatase

Smooth muscle

A. V. Sombyo

X. Wu

Electronic name

p

[Thesis]

276903

a

Y