Analysis of information sources in references of the Wikipedia article "3-Iodothyronamine" in English language version.
In this study, we investigated the action of T1AM at TAAR1 on dopaminergic terminals as compared to those of TAs. However, T1AM is also known to be an agonist of TAAR5 (Dinter et al., 2015c). Moreover, the β-phenylethylamine-like structure affords T1AM the ability to bind with various members of GPCR superfamily and ion channels (Chiellini et al., 2017; Khajavi et al., 2017). It is indeed claimed that T1AM interacts with α2a adrenergic receptors, β2-adrenergic receptors and muscarinic receptors (Kleinau et al., 2011; Dinter et al., 2015a,b; Laurino et al., 2016, 2017). Notably, outside the CNS, T1AM has been found to differentially regulate insulin secretion through actions at TAAR1 and α2a adrenergic receptor (Chiellini et al., 2017; Lehmphul et al., 2017). Hence, despite blockade of the actions of T1AM in KO mice and by pharmacological antagonist, the possibility that it exerts actions via other mechanisms should not be excluded.
One way in which TAAR1 regulates presynaptic dopamine function is by modulating phosphorylation levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis [59]. TH phosphorylation on serine (Ser) residues Ser19 [calmodulin-dependent protein kinase II (CaMKII)-targeted], Ser31 and Ser40 (PKA-targeted) determines its activity, and Ser40 phosphorylation is thought to be the main contributor to increasing TH activity and consequently dopamine production [60,61]. [...] TAAR1-KO mice display increased levels of phosphorylated TH at all three sites as well as elevated TH activity in the striatum, despite no change in overall TH protein or mRNA levels in this region [41]. [...] The TAs tyramine and PEA decrease Ser40 phosphorylation in mouse dorsal striatum, whereas 3-iodothyronamine (T1AM) increases TH phosphorylation at Ser19 and Ser40, as well as the production of the dopamine precursor l-dihydroxyphenylalanine (l-DOPA) [63]. Endogenous T1AM, however, is only found in the periphery, and its role in TAAR1 function in the brain is therefore unclear [63]. The TAAR1 antagonist EPPTB reduces CaMKII activity in the nucleus accumbens (NAc), but TH phosphorylation was not investigated in this study, and it therefore remains unclear what effect antagonism has on TH [64].
Intraperitoneal or icv injection of low doses of 3-T1AM (4 and 1.2 mol/kg body weight, respectively) into rats or mice caused a significant increase in food intake without affecting oxygen consumption and locomotor activity. However, at high 3-T1AM doses (50 mg/kg body weight, 127 mol), the authors confirmed the previously reported reduction of oxygen consumption and locomotor activity (3).
In this study, we investigated the action of T1AM at TAAR1 on dopaminergic terminals as compared to those of TAs. However, T1AM is also known to be an agonist of TAAR5 (Dinter et al., 2015c). Moreover, the β-phenylethylamine-like structure affords T1AM the ability to bind with various members of GPCR superfamily and ion channels (Chiellini et al., 2017; Khajavi et al., 2017). It is indeed claimed that T1AM interacts with α2a adrenergic receptors, β2-adrenergic receptors and muscarinic receptors (Kleinau et al., 2011; Dinter et al., 2015a,b; Laurino et al., 2016, 2017). Notably, outside the CNS, T1AM has been found to differentially regulate insulin secretion through actions at TAAR1 and α2a adrenergic receptor (Chiellini et al., 2017; Lehmphul et al., 2017). Hence, despite blockade of the actions of T1AM in KO mice and by pharmacological antagonist, the possibility that it exerts actions via other mechanisms should not be excluded.
One way in which TAAR1 regulates presynaptic dopamine function is by modulating phosphorylation levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis [59]. TH phosphorylation on serine (Ser) residues Ser19 [calmodulin-dependent protein kinase II (CaMKII)-targeted], Ser31 and Ser40 (PKA-targeted) determines its activity, and Ser40 phosphorylation is thought to be the main contributor to increasing TH activity and consequently dopamine production [60,61]. [...] TAAR1-KO mice display increased levels of phosphorylated TH at all three sites as well as elevated TH activity in the striatum, despite no change in overall TH protein or mRNA levels in this region [41]. [...] The TAs tyramine and PEA decrease Ser40 phosphorylation in mouse dorsal striatum, whereas 3-iodothyronamine (T1AM) increases TH phosphorylation at Ser19 and Ser40, as well as the production of the dopamine precursor l-dihydroxyphenylalanine (l-DOPA) [63]. Endogenous T1AM, however, is only found in the periphery, and its role in TAAR1 function in the brain is therefore unclear [63]. The TAAR1 antagonist EPPTB reduces CaMKII activity in the nucleus accumbens (NAc), but TH phosphorylation was not investigated in this study, and it therefore remains unclear what effect antagonism has on TH [64].
Intraperitoneal or icv injection of low doses of 3-T1AM (4 and 1.2 mol/kg body weight, respectively) into rats or mice caused a significant increase in food intake without affecting oxygen consumption and locomotor activity. However, at high 3-T1AM doses (50 mg/kg body weight, 127 mol), the authors confirmed the previously reported reduction of oxygen consumption and locomotor activity (3).
In this study, we investigated the action of T1AM at TAAR1 on dopaminergic terminals as compared to those of TAs. However, T1AM is also known to be an agonist of TAAR5 (Dinter et al., 2015c). Moreover, the β-phenylethylamine-like structure affords T1AM the ability to bind with various members of GPCR superfamily and ion channels (Chiellini et al., 2017; Khajavi et al., 2017). It is indeed claimed that T1AM interacts with α2a adrenergic receptors, β2-adrenergic receptors and muscarinic receptors (Kleinau et al., 2011; Dinter et al., 2015a,b; Laurino et al., 2016, 2017). Notably, outside the CNS, T1AM has been found to differentially regulate insulin secretion through actions at TAAR1 and α2a adrenergic receptor (Chiellini et al., 2017; Lehmphul et al., 2017). Hence, despite blockade of the actions of T1AM in KO mice and by pharmacological antagonist, the possibility that it exerts actions via other mechanisms should not be excluded.
