Education: Christian Medical College Hospital, Vellore, India
Research Interests: Pharmacology and Molecular Neurobiology of Monoamine Transporters
Mood disorders like anxiety, depression and drug
addiction are often linked to cardiovascular diseases, and the best way to
ultimately develop effective therapeutics is through better understanding of
the basic biological mechanisms involved. The catecholamine norepinephrine
(NE) governs multiple functions from mood, attention, arousal, and memory to
cardiovascular control. Plasma membrane NE transporter (NET) is the primary
regulator of NE signaling and a target for medications used in the treatment
of depression and ADHD as well as for psychostimulant drugs. The overall
goal of our research program is to determine the role of amine transporter
phosphorylation in normal and pathophysiological settings. Both NE and
neurokinin signals are implicated in cardiovascular diseases and mood
disorders. In this regard, part of our research effort is focused on
understanding the link between neurokinin signaling and NET modulation.
Tricyclic antidepressants, and psychostimulants such as cocaine and
amphetamine bind to amine transporters and differentially modulate transport
function. These actions are attributed to the rewarding effects and abuse liability of
these drugs. In this regard, our laboratory has been focused on
understanding the differential regulation of NET by psychostimulants. Our
research findings and studies of amine transporter phosphorylation represent
a fundamental shift in the understanding of mechanisms underlying the
actions of drugs of abuse and drug-addiction.
Arapulisamy, O., Mannangatti, P., and Jayanthi, L.D. Regulated norepinephrine transporter interaction with the neurokinin-1receptor establishes transporter subcellular localization. J. Biol. Chem. 288:28599-28610, 2013.
Annamalai, B., Mannangatti, P., Arapulisamy, O., Shippenberg, T.S., Jayanthi, L.D., Ramamoorthy, S. Tyrosine phosphorylation of the human serotonin transporter: a role in the transporter stability and function. Mol. Pharmacol. 81:73-85, 2012.
Ramamoorthy, S., Shippenberg, T.S., Jayanthi, L.D. Regulation of monoamine transporters: Role of transporter phosphorylation. Pharmacol Ther. 129:220-38, 2011.
Mannangatti, P., Arapulisamy, O., Shippenberg, T.S., Ramamoorthy, S., Jayanthi, L.D. Cocaine up-regulation of the norepinephrine transporter requires threonine 30 phosphorylation by p38 mitogen-activated protein kinase. J. Biol. Chem. 286:20239-50,2011.
Ramamoorthy, S., Samuvel, D.J., Balasubramaniam, A., See, R.E., Jayanthi, L.D. Altered dopamine transporter function and phosphorylation following chronic cocaine self-administration and extinction in rats. Biochem Biophys Res Commun. 391:1517-21, 2010.
Annamalai, B., Mannangatti, P., Arapulisamy, O., Ramamoorthy, S., Jayanthi, L.D. Involvement of threonine 258 and serine 259 motif in amphetamine-induced norepinephrine transporter endocytosis. J. Neurochem. 115:23-35, 2010.