Renuka, T R; Ani Das, V; Paulose, C S(Department of Biotechnology, March 2, 2004)
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Abstract:
Muscarinic M1 and M3 receptor changes in the brain stem during pancreatic regeneration were investigated.
Brain stem acetylcholine esterase activity decreased at the time of regeneration . Sympathetic activity also
decreased as indicated by the norepinephrine (NE) and epinephrine (EPI) content of adrenals and also in the
plasma. Muscarinic Ml and M3 receptors showed reciprocal changes in the brain stem during regeneration.
Muscairnic M1 receptor number decreased at time of regeneration without any change in the affinity. High affinity
M3 receptors showed an increase in the number. The affinity did not show any change . The number of low affinity
receptors decreased with decreased Kd at 72 hours after partial pancreatectomy. The Kd reversed to control value
with a reversal of the number of receptors to near control value . Gene expression studies also showed a similar
change in the mRNA level of Ml and M3 receptors . These alterations in the muscarinic receptors regulate
sympathetic activity and maintain glucose level during pancreatic regeneration. Central muscarinic M1 and M3
receptor subtypes functional balance is suggested to regulate sympathetic and parasympathetic activity, which in
turn control the islet cell proliferation and glucose homeostasis.
Paulose,C S; Amee,Krishnakumar; Anu,Joseph(Department of Biotechnology, October 25, 2006)
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Abstract:
The recent developments in neurobiology have rendered new prominence
and potential to study about the structure and function of brain and related disorders.
Human behaviour is the net result of neural control of the communication between
brain cells. Neurotransmitters are chemicals that are used to relay, amplify and
modulate electrical signals between neurons and/or another cell. It mediates rapid
intercellular communication through the nervous system by interacting with cell
surface receptors. These receptors often trigger second messenger signaling pathways
that regulate the activity of ion channels. The functional balance of different
neurotransmitters such as Acetylcholine (Ach), Dopamine (DA), Serotonin (5-HT),
Norepinephrine (NE), Epinephrine (EPI), Glutamate and Gamma amino butyric acid
(GABA) regulates the growth, division and other vital functions of a normal cell /
organism (Sudha, 1998). Any change in neurotransmitters' functional balance will
result in the failure of cell function and may lead to the occurrence of diseases.
Abnormalities in the production or functioning of neurotransmitters have been
implicated in a number of neurological disorders like Schizophrenia, Alzheimer's,
Epilepsy, Depression and Parkinson's disease. Changes in central and peripheral
neuronal signaling system is also noted in diabetes, cancer, cell proliferation,
alcoholism and aging. Elucidation of neurotransmitters receptor interaction pathways
and gene expression regulation by second messengers and transcriptional factors
in health and disease conditions can lead to new small molecules for development
of therapeutic agents to improve neurological disease conditions. Increased
awareness of the global effects of neurological disorders should help health care
planners and the neurological community set appropriate priorities in research,
prevention, and management of these diseases.
Sheelu,Varghese; Bake,Shameena; Lakshmy,P S; Biju,M P; Eswar Shankar,P N; Paulose,C S; Oommen,V Oommen(Department of Bio Technology, August 27, 2001)
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Abstract:
The effects of feeding of 6-propyllhiouracil (6-I'fU) and potyunsaturatcd fatty acids (I'UFA) independently and ill
combination and administration (ip) of a single close of Iriiodothyronine (I',) (2.51ig/IOOg body wl) along with feeding of 6-
PTU and PUFA were studied in cal brain. Dopamine (DA), 5-hydroxytryplophan (5-IIl'I'), serolouin (5-Ill), 5-hydioxy indole
acetic acid (5-111AA), norepinephrine (NF) :uul ceinephrinn (I?I'l) contenls were assayed in the hypothalannls and ccrc
bral cortex regions. It was found that 6-P"l'U Iccding resulted in decrease in dopamine, 5-III', 5 II I I' and 5 IIiAA in both
regions. In animals fed wills PUFA followed by adnliuislralion of T,. the I)A level was found normal.
Balarama Kaimal,S; Gireesh,G; Paulose,C S(Department of Biotechnology, January 4, 2007)
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Abstract:
Gamma amino outyric acid is a major
inhibitory neurotrarsr titter in the central nervous
system. In the preset study sv, Have investigate(' the
alteration of GABA receptor, In t he hrain stem of rats
during pancreatic regeneration. Three groups of rats
were used for the study: sham operated, 72 It and
7 days partially pancreatectonnsea. GABA was (juan-
(ified by [H]GABA receptor iispiacement method.
GABA receptor kin: 10, pat at i et•ers were studied by
using the binding of F'.](iAhA as ligand to the Triton
X-100 treated me,i1,;-:mes a1,J displacement with
unlabelled GABA. GhRA,v receptor activity was
studied by using the [` -1 h3cuculline and displacement
with unlabellecV euculline. ;.\13A content significantly
decreased (1' < (1.(101 ) it, 0-e brain stern during
the regeneration of pancreas. 'I hl, high affinity (IAI3A
receptor binding sho?:ed it sigii'f cant decrease in 131„.,\
(P < 11.01) and K,I 1).05) n 72 h and 7 days after
partial pancreatee 'timv. ";:flhicuculline hin(Iing
showed it signih eat, 'le ( r(, :,e in /Jn1,s and K,I
(P < 0.001) in 72 h pa^.rcreaw,, mised rats when compared
with sham wt--tt' as P,n and K,I reversed to
near sham after 7 da,s of pancreatectomv. The results
sugge,) that GAB A throur,r; ('GABA receptors in
brain Atcem has a regulatory uie during active regeneration
of pancreas which will have inunense clinical
significance in the treatment of cliahetcs.
Sulaiman,Pyroja; Binoy,Joseph; Paulose,C S(Department of Biotechnology, December 5, 2006)
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Abstract:
In the present study, serotonin 2C (5-HT2c) receptor binding parameters in the brainstem and cerebral cortex were investigated during
liver generation after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatic neoplasia in male Wistar rats. The
serotonin content increased significantly (p<0.01) in the cerebral cortex after PH and in NDEA induced hepatic neoplasia. Brain stem
serotonin content increased significantly (p<0.05) after PH and (p<0.001) in NDEA induced hepatic neoplasia. The number and affinity of
the 5-HT2c receptors in the crude synaptic membrane preparations of the brain stem showed a significant (p<0.001) increase after PH and in
NDEA induced hepatic neoplasia. The number and affinity of 5-HT2c receptors increased significantly (p<0.001) in NDEA induced hepatic
neoplasia in the crude synaptic membrane preparations of the cerebral cortex. There was a significant (p<0.01) increase in plasma
norepinephrine in PH and (p<0.001) in NDEA induced hepatic neoplasia, indicating sympathetic stimulation. Thus, our results suggest that
during active hepatocyte proliferation 5-HT2c receptor in the brain stem and cerebral cortex are up-regulated which in turn induce hepatocyte
proliferation mediated through sympathetic stimulation.
Jackson,James; Paulose,C S(Department of Biotechnology, May 1, 2000)
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Abstract:
5-HT2A receptor binding parameters were studied in the cerebral cortex and brain stem of
control, diabetic, insulin, insulin + tryptophan and tr3yptophan treated streptozotocin diabetic
rats. Scatchard analysis using selective antagonist, [-H](±)2,3-dimethoxyphenyl-l-[2-(4-piperidine)-
methanol] ([3H]MDL100907) in cerebral cortex of diabetic rats showed a significant
decrease in dissociation constant (Kd) without any change in maximal binding (Bm). Competition
binding studies in cerebral cortex using ketanserin against [3H]MDL100907 showed
the appearance of an additional site in the low affinity region during diabetes. In the brain
stem, Scatchard analysis showed a significant increase in Bmax and Kd. Displacement studies
showed a shift in the receptor affinity towards a low affinity state. All these altered parameters
in diabetes were reversed to control level by insulin, insulin + tryptophan and tryptophan
treatments. Tryptophan treatment is suggested to reverse the altered 5-HT2Abinding and
blood glucose level to control status by increasing the brain 5-HT content.