These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Mechanisms of positive inotropic effects and delayed relaxation produced by DPI 201-106 in mammalian working myocardium: effects on intracellular calcium handling.
    Author: Kihara Y, Gwathmey JK, Grossman W, Morgan JP.
    Journal: Br J Pharmacol; 1989 Apr; 96(4):927-39. PubMed ID: 2743084.
    Abstract:
    1. We used the bioluminescent protein aequorin, which emits light when it combines with Ca2+, to test the hypothesis that the inotropic and lusitropic actions of DPI 201-106 are due to changes in intracellular Ca2+ handling in papillary muscles from ferrets and guinea-pigs. 2. DPI 201-106 increased peak isometric tension (T) in a dose-dependent manner, with an 83% increase in T as the concentration of DPI 201-106 was increased to 1 x 10(-5) M; however, peak [Ca2+]i did not increase significantly until the concentration of DPI 201-106 reached 3 x 10(-6) M, suggesting a sensitization of the contractile apparatus to Ca2+. 3. Tetrodotoxin (1 x 10(-6) M), which did not reduce the tension response significantly before DPI 201-106, decreased both [Ca2+]i and T in the presence of 1 x 10(-5) M DPI 201-106, suggesting involvement of a sodium channel activation mechanism; however, tetrodotoxin did not completely reverse the calcium sensitization. 4. The shift of the [Ca2+]i versus T relationship was not observed in the presence of another sodium channel agonist, veratridine (3 x 10(-7)-1 x 10(-6) M). 5. In the guinea-pig, DPI 201-106 markedly prolonged relaxation of tension (increase of 60% in the time from peak to 50% tension regression), which was accompanied by the appearance of a second component in the aequorin light signal; effects on relaxation were less prominent in the ferret. 6. Tension prolongation and the second component of the [Ca2+]i transient in the guinea-pig were exacerbated by increased [Ca2+]o and decreased by tetrodotoxin. Ryanodine (3 x 10(-7) M) markedly diminished the calcium transient in controls and the initial component of the calcium transient in the presence of DPI 201-106, but had only a modest effect on the second component. 7. We conclude that although sodium agonism plays a role, sensitization of the contractile apparatus to Ca2+ is an important mechanism in the positive inotropic action of DPI 201-106. 8. The negative lusitropic action of DPI 201-106 varies between ferret and guinea-pig, possibly reflecting differences between these two species in subcellular Ca2+ handling.
    [Abstract] [Full Text] [Related] [New Search]