Linked Life Data

1719369

Source:http://linkedlifedata.com/resource/pubmed/id/1719369

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1991-12-19
pubmed:abstractText
The pharmacological, radioligand binding, and electrophysiological properties of FPL 64176, a new nondihydropyridine Ca2+ channel activator, were studied in rat tail artery, cardiac membranes, and A7r5 smooth muscle cells. FPL 64176 induced a contractile response, with an EC50 value of 2.11 x 10(-7) M. The maximum tension response to FPL 64176 was approximately 2-fold higher than that to (S)-Bay K 8644. FPL 64176 showed no significant inhibitory activity at concentrations up to 10(-5) M. The Ca2+ channel antagonists nifedipine, verapamil and diltiazem noncompetitively antagonized and completely relaxed the responses induced by FPL 64176. IC50 values of these three drugs were 5.22 x 10(-9), 1.31 x 10(-7), and 1.95 x 10(-7) M, respectively, for relaxing submaximum contractile responses to FPL 64176 (5 x 10(-7) M). The washout time for FPL 64176 was about 40 min, which was much longer than that for (S)-Bay K 8644 (within 1 min). FPL 64176 weakly inhibited (+)-[3H]PN 200-110, [3H]D888, and [3H]TA-3090 binding in rat cardiac membranes, with IC50 values of 1.04 x 10(-5) M and 7.03 x 10(-6) M for inhibition of (+)-[3H]PN 200-110 and [3H]TA-3090 binding, respectively, and with 23% inhibition of [3H]D888 binding at a FPL 64176 concentration of 1 x 10(-5) M. Dissociation kinetics of the three radioligands were allosterically accelerated by FPL 64176. Electrophysiological studies on the A7r5 smooth muscle cell line directly confirmed a large (approximately 14-fold) stimulatory effect on L-type Ca2+ current amplitude. The results suggest that FPL 64176 is a new type of Ca2+ channel activator with higher efficacy and a mechanism and site of action that are distinct from those for (S)-Bay K 8644.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
734-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Pharmacological, radioligand binding, and electrophysiological characteristics of FPL 64176, a novel nondihydropyridine Ca2+ channel activator, in cardiac and vascular preparations.
pubmed:affiliation
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't