D2 receptors

[beeitchness]

I thought I understood this very well but now I am confused.

Page 498 of 2012 FA states that antipsychotics (D2 antagonists) block dopamine D2 receptors leading to INCREASE of cAMP. This makes sense, since D2 receptors would decrease cAMP via Gi when it is "activated", therefore blocking D2 will increase cAMP.

Now, on page 438 of 2012 FA, it shows dopamine input from SNc to INHIBIT the D2 receptor. Does this ALSO cause an INCREASE of cAMP too, just like D2 antagonists?

If dopamine inhibits D2 just like the antipsychotics, then then why do they have opposite effects?
Antipsychotics cause parkinsonism symptoms when they inhibit D2, yet dopamine input on D2 will increase movement/oppose parkinsonism.

Does this mean dopamine actually activates D2 receptors, not "inhibit" them as FA says?

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[lemonade90]

I thought I understood this very well but now I am confused.

Page 498 of 2012 FA states that antipsychotics (D2 antagonists) block dopamine D2 receptors leading to INCREASE of cAMP. This makes sense, since D2 receptors would decrease cAMP via Gi when it is "activated", therefore blocking D2 will increase cAMP.

Now, on page 438 of 2012 FA, it shows dopamine input from SNc to INHIBIT the D2 receptor. Does this ALSO cause an INCREASE of cAMP too, just like D2 antagonists?

If dopamine inhibits D2 just like the antipsychotics, then then why do they have opposite effects?
Antipsychotics cause parkinsonism symptoms when they inhibit D2, yet dopamine input on D2 will increase movement/oppose parkinsonism.

Does this mean dopamine actually activates D2 receptors, not "inhibit" them as FA says?

D1=works via increasing cAMP, D2 works via decreasing cAMP. On 438 D2 is not inhibited by dopamine, rather dopamine is inhibiting the indirect pathway via decreasing cAMP. The diagram is terrible.

Scroll down to the colorful pathway in this thread (I believe its from Purves?): http://forums.studentdoctor.net/showthread.php?t=908421

 

[ipizzy]

I thought I understood this very well but now I am confused.

Page 498 of 2012 FA states that antipsychotics (D2 antagonists) block dopamine D2 receptors leading to INCREASE of cAMP. This makes sense, since D2 receptors would decrease cAMP via Gi when it is "activated", therefore blocking D2 will increase cAMP.

Now, on page 438 of 2012 FA, it shows dopamine input from SNc to INHIBIT the D2 receptor. Does this ALSO cause an INCREASE of cAMP too, just like D2 antagonists?

If dopamine inhibits D2 just like the antipsychotics, then then why do they have opposite effects?
Antipsychotics cause parkinsonism symptoms when they inhibit D2, yet dopamine input on D2 will increase movement/oppose parkinsonism.

Does this mean dopamine actually activates D2 receptors, not "inhibit" them as FA says?

Dopamine is inhibitory at D2 receptors and leads to increased movement.

Lack of dopamine in Parkinson's leads to less inhibition of D2, leading to less movement.

Antipsychotics also block dopamine from acting at D2 (in effect causing functional dopamine deficiency like Parkinson's), which yields less movement (EPS side effects). Hope this makes sense!

 

[Morsetlis]

Dopamine is activating the D2 G-protein coupled receptor, which leads to activation of the Gi subunit, which is inhibitory to AC, which leads to lowered cAMP levels reduced exocytosis of GABA from GABAnergic neurons projecting from the Striatum to the Globus Pallidus externa (GPe) of the indirect (negative feedback) pathway of the basal ganglia circuit.

Dopamine, likewise, activates the D1 GPCR, which leads to activation of the Gs subunit, which is activating to AC, which leads to increased cAMP levels and increased exocytosis of GABA from GABAnergic neurons projecting from the Striatum to the Globus Pallidus interna (GPi) of the direct (positive feedback) pathway of the basal ganglia circuit.

THUS, Dopamine is facilitating the Direct pathway, and inhibiting the Indirect pathway, via activation of D1-R on the GABAnergic striatal neurons of the direct pathway, and via activation of D2-R on the GABAnergic striatal neurons of the indirect pathway.

Dopamine does not inhibit Dopamine receptors, because it is a Dopamine-receptor agonist. If it were inhibitory, it would be a Dopamine-receptor antagonist, called Haloperidol (a drug).

 

[beeitchness]

Dopamine is activating the D2 G-protein coupled receptor, which leads to activation of the Gi subunit, which is inhibitory to AC, which leads to lowered cAMP levels reduced exocytosis of GABA from GABAnergic neurons projecting from the Striatum to the Globus Pallidus externa (GPe) of the indirect (negative feedback) pathway of the basal ganglia circuit.

Dopamine, likewise, activates the D1 GPCR, which leads to activation of the Gs subunit, which is activating to AC, which leads to increased cAMP levels and increased exocytosis of GABA from GABAnergic neurons projecting from the Striatum to the Globus Pallidus interna (GPi) of the direct (positive feedback) pathway of the basal ganglia circuit.

THUS, Dopamine is facilitating the Direct pathway, and inhibiting the Indirect pathway, via activation of D1-R on the GABAnergic striatal neurons of the direct pathway, and via activation of D2-R on the GABAnergic striatal neurons of the indirect pathway.

Dopamine does not inhibit Dopamine receptors, because it is a Dopamine-receptor agonist. If it were inhibitory, it would be a Dopamine-receptor antagonist, called Haloperidol (a drug).

Thanks - FA misled me to believing dopamine directly inhibited the D2 receptor but this cleared it up