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

2002 ◽  
Vol 80 (6) ◽  
pp. 578-587 ◽  
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 (10–9 to 10–5 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.

The Negative Inotropic Effect of β3-Adrenoceptor Stimulation in the Beating Guinea Pig Heart

2000 ◽  
Vol 35 (5) ◽  
pp. 786-790 ◽  
Author(s):  
Tetsuya Kitamura ◽  
Katsuya Onishi ◽  
Kaoru Dohi ◽  
Tsutomu Okinaka ◽  
Naoki Isaka ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Guinea Pig Heart

scholarly journals Negative Inotropic Effect of Diazepam in Isolated Guinea Pig Heart.

2001 ◽  
Vol 63 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Yukio HARA ◽  
Hiroe KOBAYASHI ◽  
Satomi OOSHIRO ◽  
Keisuke FUTAMURA ◽  
Takeshi NISHINO ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Guinea Pig Heart

Roles of PKA, PI3K, and cPLA2 in the NO-mediated negative inotropic effect of β2-adrenoceptor agonists in guinea pig right papillary muscles

2008 ◽  
Vol 294 (1) ◽  
pp. C106-C117 ◽  
Author(s):  
Fabien A. Faucher ◽  
François E. Gannier ◽  
Jacques M. Lignon ◽  
Pierre Cosnay ◽  
Claire O. Malécot
Keyword(s):  
Guinea Pig ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Guinea Pig Heart ◽  
Inotropic Effects ◽  
Inotropic State ◽  
No Release ◽  
High Concentrations

Although β2-adrenoceptors represent 15–25% of β-adrenoceptors in the guinea pig heart, their functionality is controversial. We assessed the inotropic effects of β2-adrenoceptor partial agonists in right papillary muscles. Salbutamol induced a small but significant concentration-dependent negative inotropic effect (NIE, −5% at 60 nM) followed by a moderate positive inotropic effect (+36% at 6 μM) due to activation of β1-adrenoceptors. In the presence of 4 μM atenolol, the concentration-dependent NIE (−12% at 6 μM) was biphasic, best described by a double logistic equation with respective EC50 values of 3 and ∼420 nM, and was insensitive to SR59230A. In muscles from pertussis toxin-treated guinea pigs, the salbutamol-induced positive inotropic effect was sensitive to low concentrations of ICI-118551 in an unusual manner. Experiments in reserpinized animals revealed the importance of the phosphorylation-dephosphorylation processes. PKA inhibition reduced and suppressed the effects obtained at low and high concentrations, respectively, indicating that its activation was a prerequisite to the NIE. The effect occurring at nanomolar concentrations depended upon PKA/phosphatidylinositol 3-kinase/cytosolic phospholipase A2 (cPLA2) activations leading to nitric oxide (NO) release via the arachidonic acid/cyclooxygenase pathway. NO release via PKA-dependent phosphorylation of the receptor was responsible for the inotropic effect observed at submicromolar concentrations, which is negatively controlled by cPLA2. The possibility that these effects are due to an equilibrium between different affinity states of the receptor (Gs/Gi coupled and Gi independent with different signaling pathways) that can be displaced by ICI-118551 is discussed. We conclude that β2-adrenoceptors are functional in guinea pig heart and can modulate the inotropic state.

Relationship between the Effect on Calcium Turnover and Early Cardiotoxicity of Doxorubicin and 4'-EPI-Doxorubicin in Guinea Pig Heart Muscle

1980 ◽  
Vol 66 (6) ◽  
pp. 689-697 ◽  
Author(s):  
Fabrizio Villani ◽  
Luigia Favalli ◽  
Francesco Piccinini
Keyword(s):  
Guinea Pig ◽  
Heart Muscle ◽  
Myocardial Contractility ◽  
Negative Inotropic Effect ◽  
Experimental Models ◽  
Inotropic Effect ◽  
General Mechanism ◽  
Guinea Pig Heart ◽  
Membrane Bound ◽  
Guinea Pig Atria

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.

scholarly journals Extract from leaf of Psidium guajava L depresses the guinea pig atrial contractility by interfering with potassium and calcium channels

2009 ◽  
Vol 45 (3) ◽  
pp. 483-489
Author(s):  
Antonio Nei Santana Gondim ◽  
Vanda Rodrigues de Oliveira ◽  
Sellyanna Domeny dos Santos ◽  
Bagnólia Araújo da Silva ◽  
Carla Maria Lins de Vasconcelos ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Cardiac Tissue ◽  
Negative Inotropic Effect ◽  
Psidium Guajava ◽  
Inotropic Effect ◽  
Myocardial Cells ◽  
Action Mechanism ◽  
Aqueous Fraction ◽  
Effect Curve ◽  
The Right

The negative inotropic effect of aqueous fraction (AqF) obtained from the acetic extract of Psidium guajava L leaf was investigated on the guinea pig left atrium. Myocardial force was measured isometrically (27 ± 0.1 ºC, 2 Hz). AqF (100 μg/ml) reduced contractility of about 85 ± 9.4 % (n = 4, p < 0.001, Fcalc = 51.70, F(0.01; 4; 21) = 5.09, EC50 = 14.28 ± 3 μg/mL) in a concentration-dependent fashion. This effect was reduced by 20 mM of tetraethylammonium (TEA), increasing EC50 to 50 ± 7 μg/ml (n = 4, p < 0.001, Fcalc = 282.13; F(0.01; 21; 66) = 2.36). AqF (100 μg/ml) shifted to the right the CaCl2 concentration-effect curve, increasing the EC50 from 2170 ± 112 to 2690 ± 132 μM (n = 3, p < 0.001, Fcalc = 220.80 ; F(0.01; 29; 60) = 2.19). L-NAME (100 μM) did not modify the AqF inotropic effect (n = 3, p > 0.05) sugesting that the oxide nitric pathway did not participate of the action mechanism of AqF. We can conclude that AqF depresses the atrial contractile by reducing the calcium entry in myocardial cells and also by openenig potassium channels of cardiac tissue.

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

1987 ◽  
Vol 65 (9) ◽  
pp. 1832-1839 ◽  
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.

scholarly journals Potentiation of the negative inotropic effect of adenosine on guinea pig atria by cinepazide.

1980 ◽  
Vol 30 ◽  
pp. 133
Author(s):  
Hideki Moritoki ◽  
Shinji Fujita ◽  
Masao lakei ◽  
Yukio Ishida ◽  
Akira Akashi
Keyword(s):  
Guinea Pig ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Guinea Pig Atria

Blockade of Cardiac Histamine Receptors by Promethazine

1974 ◽  
Vol 52 (1) ◽  
pp. 23-27 ◽  
Author(s):  
John H. McNeill ◽  
Subhash C. Verma
Keyword(s):  
Cyclic Amp ◽  
Guinea Pig ◽  
Histamine Receptors ◽  
Inotropic Effect ◽  
Guinea Pig Heart ◽  
Chronotropic Effects ◽  
Non Equilibrium

The inotropic and chronotropic effects of histamine on the isolated perfused guinea pig heart were antagonized by promethazine over a concentration range 4 × 10−6 – 16 × 10−6 M. Promethazine (4 × 10−6 M) decreased the ability of histamine (1 μg) to elevate cardiac cyclic AMP. A higher dose of histamine could not overcome the promethazine blockade. Promethazine (4 × 10− 6 M) did not block the inotropic effect of noradrenaline. Higher concentrations of promethazine, particularly 16 × 10−6 M did decrease the noradrenaline response. The data indicate that promethazine can interact with cardiac histamine receptors but the interaction is either noncompetitive or competitive non-equilibrium in nature.

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