Linked Life Data

8301561

Source:http://linkedlifedata.com/resource/pubmed/id/8301561

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-3-10
pubmed:abstractText
To define the minimal structural requirements for cardiac activity of thyroid hormone analogs, a series of substituted phenols were screened for their ability to bind bacterially expressed thyroid hormone receptors. Compounds with binding activity then were tested for their ability to induce expression of alpha-myosin heavy chain mRNA in primary cultures of fetal rat cardiomyocytes, a sensitive marker for potential inotropic activity. 3,5-Diiodo-4-hydroxyphenylpropionic acid (DIHPA) was found to bind specifically to bacterially expressed alpha-1 and beta-1 thyroid hormone receptors (Kaff approximately 1 to 2 x 10(5) M-1) and to induce alpha-myosin heavy chain (EC50 approximately 5 x 10(-7)). To assess the effects of DIHPA on cardiac performance in vivo, hemodynamic measurements were made in three groups of hypothyroid rats treated for 5 days with s.c. doses of DIHPA (15 mg/100 g), L-thyroxine (T4, 1.5 micrograms/100 g) or saline. Compared to controls, DIHPA and T4 produced increases in heart rate, left ventricular +dP/dtmax, -dP/dtmax, and isovolumic relaxation. In isometric papillary muscles preparations, DIHPA and T4 shortened time-to-peak tension and time-from-peak tension to 50% decline as compared with saline-treated controls. Muscles from both drug-treatment groups showed similar responses to graded doses of isoproterenol (10(-8) to 10(-3) M) and to variations in Ca++ concentration of the muscle bath (0.3125 to 3.75 x 10(-3) M). Thus, DIHPA is a novel thyromimetic compound with effects on myocardial function similar to those observed with T4.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
216-23
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Identification of simple substituted phenols with thyromimetic activity: cardiac effects of 3,5-diiodo-4-hydroxyphenylpropionic acid.
pubmed:affiliation
Department of Cardiology, Tucson Veterans Administration Medical Center, Arizona.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't