Decreased 5-HT1A Receptor Gene Expression and 5-HT1A Receptor Protein in the Cerebral Cortex and Brain Stem during Pancreatic Regeneration in Rats

Mohanan, Valiya Veettil; Kaimal, S. Balarama; Paulose, C S

doi:10.1007/s11064-004-9682-7

Cited by 20 publications

(13 citation statements)

References 38 publications

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“…The role of hypothalamic GABAergic neurotransmission in regulating sympathetic system during liver regeneration has also been reported from our laboratory [17]. Also, the decreased 5-HT 1A and 5-HT 2C receptor binding in the cerebral cortex and brain stem was reported which is stimulatory to insulin release mediated through the sympathetic system in pancreatic regeneration [18,19]. Though many reports are there implicating the brain control of pancreatic function how the central a 1 -adrenergic receptors respond to pancreatic regeneration is not well studied.…”

Section: Introductionsupporting

confidence: 62%

“…Insulin can stimulate b-cell replication directly possibly through a receptor for multiplication stimulating activity or another insulin like growth factor [32]. Tritiated thymidine incorporation studies from our laboratory [18] and previous reports showed that the DNA synthesis in pancreatic islets was maximum at 72 h after pancreatectomy i.e. during active pancreatic regeneration [20,33].…”

Section: Discussionmentioning

confidence: 92%

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Decreased α1-Adrenergic Receptor Binding in the Cerebral Cortex and Brain Stem during Pancreatic Regeneration in Rats

2006

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The purpose of this study was to investigate the role of brain alpha1-adrenergic receptor binding in the rat model of pancreatic regeneration using 60-70% pancreatectomy. The alpha1-adrenergic receptors kinetics was studied in the cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [3H]prazosin in cerebral cortex and brain stem showed a significant decrease (P < 0.01), (P < 0.05) in maximal binding (Bmax) with a significant decrease (P < 0.001), (P < 0.01) in the Kd in 72 h pancreatectomised rats compared with sham respectively. Competition analysis in cerebral cortex and brain stem showed a shift in affinity during pancreatic regeneration. The sympathetic activity was decreased as indicated by the significantly decreased norepinephrine level in the plasma (P < 0.001), cerebral cortex (P < 0.01) and brain stem (P < 0.001) of 72 h pancreatectomised rats compared to sham. Thus, from our results it is suggested that the central alpha1-adrenergic receptors have a functional role in the pancreatic regeneration mediated through the sympathetic pathway.

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Section: Introductionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 92%

Decreased α1-Adrenergic Receptor Binding in the Cerebral Cortex and Brain Stem during Pancreatic Regeneration in Rats

2006

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“…Tritiated thymidine incorporation studies from our laboratory [21] and previous reports showed that the DNA synthesis in pancreatic islet was maximum at 72 It after pancreatectomy i.e. during active pancreatic regeneration.…”

Section: Discussionmentioning

confidence: 53%

Decreased 5-HT2C receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats

2005

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The purpose of this study was to investigate the role of central 5-HT2C receptor binding in rat model of pancreatic regeneration using 60-70% pancreatectomy. The 5-HT and 5-HT2c receptor kinetics were studied in cerebral cortex and brain stem of sham operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [3H] mesulergine in cerebral cortex showed a significant decrease (p < 0.05) in maximal binding (B^,ax) without any change in Kd in 72 h pancreatectomised rats compared with sham. The decreased Bmax reversed to sham level by 7 days after pancreatectomy. In brain stem , Scatchard analysis showed a significant decrease (p < 0.01) in Bax with a significant increase (p < 0.01) in Kd. Competition analysis in brain stem showed a shift in affinity towards a low affinity. These parameters were reversed to sham level by 7 days after pancreatectomy. Thus the results suggest that 5-HT through the 5-HT2C receptor in the brain has a functional regulatory role in the pancreatic regeneration. (Mol Cell Biochem 272: 165-170, 2005)

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“…The increased sympathetic stimulation leads to hypertension in pyridoxine deficient rats [5], which in turn lead to diabetes [8]. The decreased binding of the 5-HT 1A and 5-HT 2C receptors in the cerebral cortex and brain stem during pancreatic regeneration suggests the stimulatory role of insulin secretion mediated through the sympathetic system [11,12]. The muscarinic M1 receptor in the brain stem decreased at 72 h after partial pancreatectomy and M3 receptors increased at the time of pancreatic regeneration.…”

Section: Discussionmentioning

confidence: 99%

“…Vagal stimulation is involved in the sensitization of islets to physiological elevated levels of glucose concentrations [4]. Earlier studies from our laboratory have established the central neurotransmitter receptor subtypes functional regulation during pancreatic regeneration, diabetes and cell proliferation [5][6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Increased Insulin Secretion by Muscarinic M1 and M3 Receptor Function from Rat Pancreatic Islets in vitro

2006

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Cell's behaviours of like growth, motility, differentiation and apoptosis are regulated by signals received from their environment. These extracellular signaling molecules include neurotransmitters, hormones and growth factors which regulate the activation of intracellular signaling pathways leading to changes in gene expression and cell fate. Cholinergic system through muscarinic M1 and M3 receptors play an important role in the regulation of pancreatic b-cell proliferation and insulin secretion. Cholinergic activity was decreased in the brain regions-hypothalamus, brain stem, corpus striatum, cerebral cortex and cerebellum during pancreatic regeneration. Muscarinic M1 receptors were decreased at time of regeneration while M3 receptors showed an increase. Gene expression studies confirmed the mRNA level of M1 and M3 receptors. These changes in the muscarinic receptors regulate sympathetic activity and maintain glucose level. Pancreatic muscarinic M1 and M3 receptor activity were increased during proliferation indicating that both receptors are stimulatory to pancreatic b-cell division. Acetylcholine dose dependently increased EGF induced DNA synthesis in pancreatic islets in vitro which is inhibited by muscarinic antagonist atropine confirming the role of muscarinic receptors. Acetylcholine also stimulated glucose induced insulin secretion in vitro which is inhibited by muscarinic M1 and M3 receptor antagonists. Thus it is suggested that central muscarinic M1 and M3 receptor subtypes functional difference regulates sympathetic and parasym-pathetic systems which control the islet cell proliferation and glucose homeostasis. Hydroxymethylglutaryl-coenzyme reductase inhibitors (statins) are widely used clinically to reduce serum low density lipoprotein but little is known about their effects in the central nervous system. Sprague-Dawley rats were administered simvastatin or pravastatin (10 mg, p.o.) once daily for 4 weeks. Serum triglyceride levels were similarly reduced in the simvastatin-treated (45%) and pravastatin-treated (48%) groups. Serum cholesterol levels, however, remained unchanged in both groups. Simvastatin treatment increased the expression of eNOS, D1 and D2 receptors at both mRNA (2.1-fold, 1.6-fold and 2.2-fold, respectively) and protein (1.8-fold, 1.3-fold and 1.5-fold, respectively) levels in the frontal cortex, but not in the striatum. Similar changes were not observed in the frontal cortex of the pravastatin-treated rats. There were also no observable changes in the expression of nNOS and iNOS in simvastatin-treated rats. These results suggest that lipophilic statins can alter dopaminergic functions via a central mechanism. Thus, their use may have important implications in the brain reward and reinforcing circuits as well as in disease states associated with dopaminergic abnormality. It is tempting to suggest that the up-regulation eNOS and the two dopamine receptors may be linked in a cause-effect relationship after simvastatin treatment. Prostaglandin E 2 (PGE 2) is a well established hyper...

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Decreased 5-HT1A Receptor Gene Expression and 5-HT1A Receptor Protein in the Cerebral Cortex and Brain Stem during Pancreatic Regeneration in Rats

Cited by 20 publications

References 38 publications

Decreased α1-Adrenergic Receptor Binding in the Cerebral Cortex and Brain Stem during Pancreatic Regeneration in Rats

Decreased α1-Adrenergic Receptor Binding in the Cerebral Cortex and Brain Stem during Pancreatic Regeneration in Rats

Decreased 5-HT2C receptor binding in the cerebral cortex and brain stem during pancreatic regeneration in rats

Increased Insulin Secretion by Muscarinic M1 and M3 Receptor Function from Rat Pancreatic Islets in vitro

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