CAMP formation dopamine

Five subtypes of dopamine receptors have been described they are the Dj-like and Dj-like receptor groups. All have seven transmembrane domains and are G protein-coupled. The Dj-receptor increases cyclic adenosine monophosphate (cAMP) formation by stimulation of dopamine-sensitive adenylyl cyclase it is located mainly in the putamen, nucleus accumbens, and olfactory tubercle. The other member of this family is the D5-receptor, which also increases cAMP but has a 10-fold greater affinity for dopamine and is found primarily in limbic regions. The therapeutic potency of antipsychotic drugs does not correlate with their affinity for binding to the Dj-receptor. 

In other cell types, guanine nucleotides interact with a guanine nucleotide subunit (G- or Ng-subunit) to translate receptor stimulation into increased adenylate cyclase activity (12.) Cholera toxin inhibits a specific GTPase on this guanine nucleotide subunit and thereby increases adenylate cyclase activity (13.). In dispersed cells from the bovine parathyroid gland, cholera toxin markedly increases cAMP formation and causes a 3 to 10-fold increase in the apparent affinity cf dopamine for its receptor (as determined by cAMP accumulation or IR-PTH secretion (J y.). The effects of guanine nucleotides and cholera toxin on cAMP accumulation in parathyroid cells result from interactions with the guanine nucleotide subunit in this cell. 

In fact the most important point concerns the very poor pharmacological characterization of the cAMP formation enhanced by dopamine and of the parathormone secretion. Firstly, apomorphine is much less potent than dopamine, a fact which is not compatible with what we know from pharmacological, behavioural and even biochemical studies (3,4 7) It is believed that apomorphine is a partial antagonist, but this has never been found in in vivo conditions. The higher potency of apomorphine is also reflected by its high affinity in %-haloperidol and 3H-spiperone binding. 

At the biochemical level, the actions of dopamine at D1 and D2 receptors are antagonistic, with D1 receptor stimulation stimulating cAMP formation and D2 receptor stimulation inhibiting cAMP formation. If in the same cell, both receptors are expressed... 

The ability of dopamine to increase [ H]cAMP formation in cultured striatal neurones (16-day embryos of Swiss mice) was blocked by its nitration by NO or its nitrogen oxide derivatives (Daveu et al. 1997). 

Dl-iike receptors activate the Gs transduction pathway, stimulating the production of adenylyl cyclase, which increases the formation of cyclic adenosine monophosphate (cAMP) and ultimately increases the activity of cAMP-dependent protein kinase (PKA). PKA activates DARPP-32 (dopamine and cyclic adenosine 3, 5 -monophosphate-regulated phosphoprotein, 32 kDa) via phosphorylation, permitting phospho-DARPP-32 to then inhibit protein phosphatase-1 (PP-1). The downstream effect of decreased PP-1 activity is an increase in the phosphorylation states of assorted downstream effector proteins regulating neurotransmitter... 

The dopamine-stimulated formation of cAMP may initiate the dopamine-induced release of IR-PTH. A linear relationship exists between the dopamine-induced release of IR-PTH and the logarithm of the dopamine-induced accumulation of cAMP (17). Similarly, other agents increasing cAMP accumulation and IR-PTH release (e.g. beta-adrenergic agonists, secretin and phosphodiesterase inhibitors, also display such a log-linear relationship. Additional support for the possibility that intracellular cAMP might initiate PTH secretion comes from the observations that cholera toxin (JJ.), phosphodiesterase inhibitors (17) and dibutyryl cAMP (18), agents known to increase intracellular cAMP or mimic the biochemical effects of cAMP, increase the release of IR-PTH. 

Tetrahydrobiopterin is not a vitamin, because it can be synthesized from GTP, as shown in Figure 10.2 (Thony et al., 2000). It is the coenzyme for mixed-function oxidases phenylalanine, tyrosine, and tryptophan hydroxylases alkyl glycerol monoxygenase, which catalyzes the cleavage of alkyl glycerol ethers and nitric oxide synthase in the formation of nitric oxide. In addition to its coenzyme role, tetrahydrobiopterin has a direct effect on neurons, acting to stimulate dopamine release via a cAMP-dependent protein kinase and a calcium channel (Koshimura et al., 2000). 

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