Which type of receptor is responsible for the negative inotropic effect of adenosine in guinea pig atrial heart muscle

Doxorubicin and 4'-epi-doxorubicin, two anthracycline derivatives with different cardiotoxic effects in experimental models, were found to decrease myocardial contractility in isolated guinea pig atria by significantly modifying calcium turnover. This effect seems to be mainly localized on the fast exchanging membrane-bound calcium, while these drugs do not significantly influence the intracellular stores of calcium. 4'-epi-doxorubicin, which induces a less negative inotropic effect than doxorubicin, produces a smaller inhibition of calcium turnover. This supports the hypothesis that the inhibition of calcium turnover and particularly of the fast exchanging calcium compartment is a general mechanism involved in the early anthracycline-induced cardiotoxicity.

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Functional and autoradiographic characterization of dopamine D2-like receptors in the guinea pig heart

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y02-081 ◽

2002 ◽

Vol 80 (6) ◽

pp. 578-587 ◽

Cited By ~ 14

Author(s):

María de Jesús Gómez ◽

Guy Rousseau ◽

Réginald Nadeau ◽

Roberto Berra ◽

Gonzalo Flores ◽

...

Keyword(s):

Guinea Pig ◽

Western Blot ◽

Dopamine Receptors ◽

Negative Inotropic Effect ◽

Cyclase Activity ◽

Inotropic Effect ◽

Receptor Subtypes ◽

Guinea Pig Heart ◽

Additional Information ◽

The Right

Dopamine receptors include the D1- (D1 and D5 subtypes) and D2-like (D2, D3, and D4 subtypes) families. D1-like receptors are positively and D2-like receptors negatively coupled to the adenylyl cyclase. Dopamine D2-like (D4 subtype) receptors have been identified in human and rat hearts. However the presence of D2 and D3 receptor subtypes is unclear. Furthermore, their role in cardiac functions is unknown. By autoradiographic studies of guinea pig hearts, we identified D3 and D4 receptors, using the selective radioligands [3H]-7-OH-DPAT and [3H]emonapride (YM-09151-2 plus raclopride). Western blot analysis confirmed D3 and D4 receptors in the right and left ventricle of the same species. Selective agonists of D3 and D4 receptors (±)-7-OH-DPAT and PD 168 077 (109 to 105 M, respectively) induced a significant negative chronotropic and inotropic effect in the isolated guinea pig heart preparation. Negative inotropic effect induced by PD 168 077 was associated with an inhibition in cyclase activity. No changes in cyclase activity were found with (±)-7-OH-DPAT. The aim of this study is to support the presence of D3 and D4 receptors in the heart. Although our results suggest that D3 and D4 receptors are functionally active in the heart, we need additional information with an antagonist and an agonist of improved potency and selectivity to understand the respective roles of D3 and D4 receptors in the cardiac functions.Key words: Dopamine receptors (D2, D3, D4 subtypes), autoradiography, Western blot, cAMP, heart.

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A Weak Negative Inotropic Effect of Protamine Sulfate upon the Isolated Canine Heart Muscle

Anesthesia & Analgesia ◽

10.1213/00000539-198002000-00004 ◽

1980 ◽

Vol 59 (2) ◽

pp. 100???102 ◽

Cited By ~ 7

Author(s):

Naofumi Iwatsuki ◽

Shuh Matsukawa ◽

Kenichi Iwatsuki

Keyword(s):

Heart Muscle ◽

Negative Inotropic Effect ◽

Protamine Sulfate ◽

Inotropic Effect ◽

Canine Heart

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Calcium channels and excitation–contraction coupling in cardiac cells. II. A pharmacological study of the biphasic contraction in guinea-pig papillary muscle

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y87-285 ◽

1987 ◽

Vol 65 (9) ◽

pp. 1832-1839 ◽

Cited By ~ 3

Author(s):

E. Honoré ◽

M. M. Adamantidis ◽

B. A. Dupuis ◽

C. E. Challice ◽

P. Guilbault

Keyword(s):

Guinea Pig ◽

Papillary Muscle ◽

Positive Inotropic Effect ◽

Pharmacological Study ◽

Negative Inotropic Effect ◽

Cardiac Cells ◽

Inotropic Effect ◽

Free Solution ◽

Contraction Coupling ◽

Rich Solution

Biphasic contractions were obtained in guinea-pig papillary muscle by inducing partial depolarization in K+-rich solution (17 mM) in the presence of 0.3 μM isoproterenol. Mn2+ ions inhibited the two components of contraction in a similar way. Nifedipine and particularly Cd2+ ions specifically inhibited the second component of contraction. Isoproterenol and BAY K 8644 markedly increased the amplitude of the second component (P2) of contraction. Nevertheless, a moderate positive inotropic effect of isoproterenol was found on the first component (P1) of contraction when excitability was restored by 0.2 mM Ba instead of isoproterenol. Acetylcholine and hypoxia decreased the amplitude of the second component of contraction to a greater extent. In the presence of digoxin or Na+-free solution, P1was strongly increased. When sarcoplasmic reticular function was hindered by 1 mM caffeine or in the presence of Ca2+-free Sr2+ solution, digoxin always induced a negative inotropic effect on P2. Inversely in these conditions the transient positive inotropic effect of Na+-free solution was strongly reduced. These results are consistent with the hypothesis that the late component of contraction is triggered by the slow inward Ca2+ current and that the early component is due to Ca2+ release from the sarcoplasmic reticulum.

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