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

Abstract

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.

Expression and Distribution of Dopamine Transporter in Cardiac Tissues of the Guinea Pig

“…Then dopamine has predominantly role in the control of cardiac function since it is regulating the sympathetic tone throughout regulating the release of norepinephrine from terminal sympathetic nerves. In addition others studies have been demonstrated the expression of dopamine receptors in mammal hearts [40][41][42]. Also mRNA levels for D 1 , and D 4 receptors have been reported in mammals heart including human heart [43,44].…”

A Prospective, Multicenter, 2-Year Echocardiographic Study on Valvular Heart Disease in Parkinson's Disease Patients Taking Rotigotine and Other non-Ergot Dopamine Agonists

“…Cardiovascular effects of DAs are thought to be related to the activation of dopaminergic and non-dopaminergic receptors [17,18]. D1-like and D2-like dopamine receptors located at various sites within the vascular, cardiac and renal regions have been shown to mediate cardiovascular and renal effects [19]. The different subtypes of α2-receptors regulate the norepinephrine and noradrenaline release in sympathetic neurons [20,21].…”

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP₃ Receptors in Guinea Pig Hearts

“…Monassier et al (2007) showed that haloperidol blocks human recombinant hERG potassium channels in COS-7 monkey kidney cells via stimulation of sigma 2 receptors. On the other hand, haloperidol has affinity for dopamine D 2 receptors, which are located in guinea pig heart (Gomez et al 2002). Dopamine D 2 agonists may increase QT interval duration (Gomez et al 2002).…”

“…On the other hand, haloperidol has affinity for dopamine D 2 receptors, which are located in guinea pig heart (Gomez et al 2002). Dopamine D 2 agonists may increase QT interval duration (Gomez et al 2002). However, haloperidol acts as a dopamine D 2 antagonist and the dopaminergic effect on the heart rate and QT interval duration is disputable.…”