scholarly journals Dopamine D2 Receptor-Mediated Heterologous Sensitization of AC5 Requires Signalosome Assembly

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Karin F. K. Ejendal ◽  
Carmen W. Dessauer ◽  
Terence E. Hébert ◽  
Val J. Watts
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adenylyl Cyclase ◽  
Dopamine Receptors ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Receptor Activation ◽  
Adenylyl Cyclase Activity ◽  
Central Nervous System Disorders ◽  
Heterologous Sensitization

Chronic dopamine receptor activation is implicated in several central nervous system disorders. Although acute activation of Gαi-coupled D2 dopamine receptors inhibits adenylyl cyclase, persistent activation enhances adenylyl cyclase activity, a phenomenon called heterologous sensitization. Previous work revealed a requirement for Gαs in D2-induced heterologous sensitization of AC5. To elucidate the mechanism of Gαs dependency, we expressed Gαs mutants in Gαs-deficient GnasE2−/E2− cells. Neither Gαs-palmitoylation nor Gαs-Gβγ interactions were required for sensitization of AC5. Moreover, we found that coexpressing βARKct-CD8 or Sar1(H79G) blocked heterologous sensitization. These studies are consistent with a role for Gαs-AC5 interactions in sensitization however, Gβγ appears to have an indirect role in heterologous sensitization of AC5, possibly by promoting proper signalosome assembly.

Pharmacokinetics and central nervous system effects of the novel dopamine D2 receptor antagonist JNJ-37822681

2011 ◽  
Vol 26 (8) ◽  
pp. 1119-1127 ◽  
Author(s):  
Erik T te Beek ◽  
Matthijs Moerland ◽  
Peter de Boer ◽  
Luc van Nueten ◽  
Marieke L de Kam ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Receptor Antagonist ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
The Novel ◽  
Dopamine D2 ◽  
Dopamine D2 Receptor Antagonist

Dopamine Receptors: From Structure to Function

1998 ◽  
Vol 78 (1) ◽  
pp. 189-225 ◽  
Author(s):  
CRISTINA MISSALE ◽  
S. RUSSEL NASH ◽  
SUSAN W. ROBINSON ◽  
MOHAMED JABER ◽  
MARC G. CARON
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adenylyl Cyclase ◽  
Dopamine Receptors ◽  
G Protein ◽  
Receptor Gene ◽  
Hormone Secretion ◽  
Receptor Subtypes ◽  
Genetic Linkage Analysis ◽  
G Protein Coupled

Missale, Cristina, S. Russel Nash, Susan W. Robinson, Mohamed Jaber, and Marc G. Caron. Dopamine Receptors: From Structure to Function. Physiol. Rev. 78: 189–225, 1998. — The diverse physiological actions of dopamine are mediated by at least five distinct G protein-coupled receptor subtypes. Two D1-like receptor subtypes (D1 and D5) couple to the G protein Gs and activate adenylyl cyclase. The other receptor subtypes belong to the D2-like subfamily (D2 , D3 , and D4) and are prototypic of G protein-coupled receptors that inhibit adenylyl cyclase and activate K+ channels. The genes for the D1 and D5 receptors are intronless, but pseudogenes of the D5 exist. The D2 and D3 receptors vary in certain tissues and species as a result of alternative splicing, and the human D4 receptor gene exhibits extensive polymorphic variation. In the central nervous system, dopamine receptors are widely expressed because they are involved in the control of locomotion, cognition, emotion, and affect as well as neuroendocrine secretion. In the periphery, dopamine receptors are present more prominently in kidney, vasculature, and pituitary, where they affect mainly sodium homeostasis, vascular tone, and hormone secretion. Numerous genetic linkage analysis studies have failed so far to reveal unequivocal evidence for the involvement of one of these receptors in the etiology of various central nervous system disorders. However, targeted deletion of several of these dopamine receptor genes in mice should provide valuable information about their physiological functions.

The dopamine receptor in adult and maturing kidney

1989 ◽  
Vol 257 (3) ◽  
pp. F315-F327 ◽  
Author(s):  
R. A. Felder ◽  
C. C. Felder ◽  
G. M. Eisner ◽  
P. A. Jose
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adenylate Cyclase ◽  
Dopamine Receptors ◽  
Dopamine Receptor ◽  
Receptor Activation ◽  
Receptor Subtypes ◽  
The Central Nervous System ◽  
Renal Tubular ◽  
Da2 Receptor

Dopamine, like other neurotransmitters, exerts its biological effects by occupation of specific receptor subtypes. The dopamine receptors in the central nervous system and certain endocrine organs are classified into the D1/D2 subtypes. Outside the central nervous system, the dopamine receptors are classified into the DA1/DA2 subtypes. The D1/D2 and DA1/DA2 receptor have marked similarities and some differences, the most notable of which is the lower affinity of the DA dopamine compared with the D dopamine receptor. DA1 receptor activation increases renal blood flow (RBF); stimulation of DA1 and DA2 receptors may also increase glomerular filtration rate (GFR). DA1 agonists inhibit fluid and electrolyte transport indirectly via hemodynamic mechanisms and directly by occupation of DA1 receptors in specific nephron segments. In the proximal tubule, DA1 agonists simulate adenylate cyclase and inhibit Na+-H+ antiport activity. They also increase phospholipase C and inhibit Na+-K+-ATPase activity (presumably as a consequence of protein kinase C activation). The latter effects may be facilitated by DA2 agonists. In cortical collecting ducts, dopamine antagonizes the effects of mineralocorticoids and the hydrosomotic effect of antidiuretic hormone. It has also been suggested that DA1 may also decrease sodium transport by influencing other hormones, such as atrial natriuretic peptide. Studies of dopamine in the young are complicated because of the propensity for dopamine to stimulate alpha-adrenoceptors. Dopamine alone may actually decrease RBF in the perinatal period. In some animals, the renal vasodilatory and natriuretic effects of dopamine increase with age. Renal tubular DA1-stimulated adenylate cyclase activity increases, whereas renal tubular DA1 receptors decrease with age. Renal DA2 receptor density is greater in the fetus; after birth renal DA2 receptors do not change. Endogenous dopamine may regulate sodium excretion in the young differently than in the adult. In the adult, sodium surfeit is associated with an increase in urinary dopamine; the opposite occurs in the young. A decrease in dopamine production or blockade of dopamine receptors results in an antinatriuresis in the adult; dopamine blockade in the young results in a natriuresis. It remains to be determined whether these age-related differences in dopamine effects are due to changes in receptor DA subtype density, second messengers, and/or interaction with other receptors.

Central nervous system disorders and damage: Implications for stress, anxiety, and depression

2007 ◽  
Author(s):  
P. S. Seibert ◽  
P. D. Parker ◽  
C. M. Patterson ◽  
N. Whitener ◽  
J. O'Donnell ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Anxiety And Depression ◽  
Central Nervous System Disorders
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