In the past Rishi K. Somvanshi has collaborated on articles with Padmesh S. Rajput. One of their most recent publications is Surface plasmon resonance studies and biochemical evaluation of a potent peptide inhibitor against cyclooxygenase-2 as an anti-inflammatory agent. Which was published in journal Biochemical and Biophysical Research Communications.

More information about Rishi K. Somvanshi research including statistics on their citations can be found on their Copernicus Academic profile page.

Rishi K. Somvanshi's Articles: (5)

Surface plasmon resonance studies and biochemical evaluation of a potent peptide inhibitor against cyclooxygenase-2 as an anti-inflammatory agent

AbstractCyclooxygenase (COX) is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins, which are mediators of inflammation [D.L. Dewitt, W.L. Smith, Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence, Proc. Natl. Acad. Sci. USA 85 (1988) 1412–1416, 1]. It exists mainly in two isoforms COX-1 and COX-2 [A. Raz, A. Wyche, N. Siegel, P. Needleman, Regulation of fibroblast cyclooxygenase synthesis by interleukin-1, J. Biol. Chem. 263 (1988) 3022–3028, 2]. The conventional non-steroidal anti-inflammatory drugs (NSAIDs) have adverse gastrointestinal side-effects, because they inhibit both isoforms [T.D. Warner, F. Guiliano, I. Vojnovic, A. Bukasa, J.A. Mitchell, J.P. Vane, Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis, Proc. Natl. Acad. Sci. USA 96 (1999) 7563–7568, 3; L.J. Marnett, A.S. Kalgutkar, Cyclooxygenase 2 inhibitors: discovery, selectivity and the future, Trends Pharmacol. Sci. 20 (1999) 465–469, 4; J.R. Vane, NSAIDs, Cox-2 inhibitors, and the gut, Lancet 346 (1995) 1105–1106, 5]. Therefore drugs which selectively inhibit COX-2, known as coxibs were developed. Recent reports on the harmful cardiovascular and renovascular side-effects of the anti-inflammatory drugs have led to the quest for a novel class of COX-2 selective inhibitors. Keeping this in mind, we have used the X-ray crystal structures of the complexes of the COX-1 and COX-2 with the known inhibitors for a rational, structure based approach to design a small peptide, which is potent inhibitor for COX-2. The peptides have been checked experimentally by in-vitro kinetic studies using surface plasmon resonance (SPR) and other biochemical methods. We have identified a tripeptide inhibitor which is a potential lead for a new class of COX-2 inhibitor. The dissociation constant (KD) determined for COX-2 with peptide WCS is 1.90 × 10−10 M, the kinetic constant (Ki) determined by spectrophotometry is 4.85 × 10−9 M and the IC50 value is 1.5 × 10−8 M by ELISA test.

Colocalization of dopamine receptor subtypes with dopamine and cAMP-regulated phosphoprotein (DARPP-32) in rat brain

AbstractIn the present study using indirect immunofluorescence immunohistochemistry, co-immunoprecipitation and western blot analysis we determined the colocalization of dopamine receptors 1–5 and dopamine and cAMP-regulated phosphoprotein (DARPP-32) in rat brain cortex and striatum. All five DR subtypes and DARPP-32 were expressed in rat brain cortex and striatum. DARPP-32 positive neurons displayed comparative colocalization with DR1-5. In cingulate cortex, the colocalization of DR subtypes was greatly different from frontal or temporal cortex. D1R is one of the most predominant subtypes which colocalized with DARPP-32 in cortex as well as striatum and followed by D2R, D3R, D4R and D5R. Amongst all DR subtypes D5R was coexpressed the least with DARPP-32 positive neurons. Consistent with immunohistochemical data, western blot analysis also reveals comparable distribution of DR subtypes and DARPP-32 in cortex and striatum. Colocalization studies were also supported by using co-immunoprecipitate assay displaying DARPP-32 expression in DR immunoprecipitate from tissue lysate prepared from cortex and striatum. Taken together our data support receptor specific association of DARPP-32 with DR subtypes that might shed new information in drugs of abuse and pathophysiology of neurodegenerative diseases as well as neuropsychiatric disorders such as schizophrenia.

Expression of somatostatin and somatostatin receptor subtypes in Apolipoprotein D (ApoD) knockout mouse brain: An immunohistochemical analysis

AbstractApolipoprotein D (ApoD) is widely distributed in central and peripheral nervous system. ApoD expression has been shown to increase in several neurodegenerative and neuropsychiatric disorders, as well as during regeneration in the nervous system. Like ApoD, in the central nervous system somatostatin (SST) is widely present and functions as neurotransmitter and neuromodulator. The biological effects of SST are mediated via binding to five high-affinity G-protein coupled receptors termed SSTR1–5. Mice lacking ApoD exhibit reduced SST labeling in cortex and hippocampus and increased expression in striatum and amygdala without any noticeable changes in substantia nigra. Changes in SSTRs expressions have been described in several neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's diseases. In the present study, using SSTR1–5 receptor-specific antibodies, we mapped their distribution in wild type (wt) and ApoD knockout (ApoD−/−) mouse brain. SSTR1–5 expression was observed both as membrane and cytoplasmic protein and display regions and receptor specific differences between wt and ApoD−/− mice brains. In cortex and hippocampus, SSTR subtypes like immunoreactivity are decreased in ApoD−/− mice brain. Unlike cortex and hippocampus, in the striatum of ApoD−/− mice, projection neurons showed increased SSTR immunoreactivity, as compared to wt. Higher SSTR subtypes immunoreactivity is seen in substantia nigra pars compacta (SNpc) whereas lower in substantia nigra pars reticulata (SNpr) of ApoD−/− mice brains as compared to wt. Whereas, amygdala displayed SSTR subtypes changes in different nuclei of ApoD−/− mice in comparison to wt mice brain. Taken together, our results describe receptor and region specific changes in SST and SSTR subtypes expression in ApoD−/− mice brain, which may be linked to specific neurological disorders.

C-tail mediated modulation of somatostatin receptor type-4 homo- and heterodimerizations and signaling

AbstractSomatostatin receptors show great diversity in response to agonist mediated receptor-specific homo- and heterodimerizations. Here, using photobleaching-fluorescence resonance energy transfer, immunocytochemistry, western blot and co-immunoprecipitation, we investigated dimerization, trafficking, coupling to adenylyl cyclase and signaling of human somatostatin receptor-4 (hSSTR4) in HEK-293 cells. We also determined the role of the C-tail of hSSTR4 on physiological responses of the cells. wt-hSSTR4 exogenously expressed in HEK-293 cells exhibits constitutive dimerization, inhibits forskolin-stimulated cAMP, and displays agonist dependent changes in pERK1/2 and pERK5 expressions. Upon C-tail deletion, the receptor loses membrane expression and ability to dimerize and inhibition of cAMP and pERK5 however, displays several-fold increases in the expression of pERK1/2. Chimeric hSSTR4 with the C-tail of hSSTR5 functions like wt-hSSTR4, in contrast, with the C-tail of hSSTR1 functions like C-tail deleted hSSTR4. hSSTR4 dimerization and signaling are associated with increased cyclin-dependent-kinase p27kip1 expression and inhibition of the cell proliferation. We also report heterodimerization between hSSTR4/hSSTR5, but not between hSSTR4/hSSTR1, with significant changes in receptor functions. Taken together, these data define a novel mechanism for the role of hSSTR4 in cell proliferation and modulation of signaling pathways.

Receptor specific crosstalk and modulation of signaling upon heterodimerization between β1-adrenergic receptor and somatostatin receptor-5

AbstractIn the present study we describe heterodimerization, trafficking, coupling to adenylyl cyclase and signaling in HEK-293 cells cotransfected with human-somatostatin receptor 5 (hSSTR5) and β1-adrenergic receptor (β1AR). hSSTR5/β1AR exists as heterodimers in basal conditions which was further enhanced upon synergistic activation of both receptors. Activation of either β1AR or hSSTR5 displayed dissociation of heterodimerization. In cotransfectants, β1AR effect on cAMP was predominant; however, blocking β1AR with antagonist resulted in 60% inhibition of forskolin-stimulated cAMP in the presence of hSSTR5 agonists. cAMP/PKA pathway in cotransfected cells was regulated in receptor-specific manner, in contrast, the status of pERK1/2 and pPI3K/AKT was predominantly regulated by hSSTR5. The expression levels of phosphorylated NFAT remained unchanged indicating blockade of calcineurin-mediated dephosphorylation and nuclear translocation of NFAT, the process predominantly regulated by pJNK in SSTR5 dependent manner. Taken together, the functional consequences of results described here might have relevance in the cardiovascular system where SSTR and AR subtypes play important roles.

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