Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of adrenergic blockade on hepatic venous hyperglycemia and the activation of a hepatic glycogenolytic enzyme, phosphorylase-a, in response to cerebral cholinergic activation. Neostigmine was injected into the third cerebral ventricle of bilaterally adrenodemedullectomized (ADMX) rats, while somatostatin and insulin were administered intravenously. Hepatic venous plasma glucose concentrations and hepatic phosphorylase-a activity were measured. Intracerebroventricular injection of neostigmine (5 x 10(-8) mol) caused increases in hepatic venous glucose concentrations and hepatic phosphorylase-a activity. Both of these changes were prevented by intraperitoneal (IB) pretreatment with phentolamine (5 x 10(-7), 1 x 10(-6) mol) without the intervention of insulin secretion, but not by pretreatment with the alpha-adrenoreceptor antagonist phenoxybenzamine (1 x 10(-6) mol), the beta-adrenoreceptor antagonist propranolol (1 x 10(-6) mol), the alpha 1-antagonists prazosin or bunazosin (1 x 10(-6) mol), the alpha 2-antagonist yohimbine (1 x 10(-6) mol), or prazosin (5 x 10(-7) mol) plus yohimbine (5 x 10(-7) mol). These results suggest that phentolamine prevented brain-mediated hepatic glycogenolysis by a mechanism that may not be classified pharmacologically as involving either alpha 1- or alpha 2-receptors.
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PMID:Effects of adrenergic blockers on central nervous system-mediated hyperglycemia in fed rats. 135 Mar 17

The influence of brain cholinergic activation on hepatic glycogenolysis and gluconeogenesis was studied in fed and 48-hour fasted rats. Neostigmine was injected into the third cerebral ventricle and hepatic venous plasma glucose, glucagon, insulin, and epinephrine were measured. The activity of hepatic phosphorylase-a and phosphoenolpyruvate-carboxykinase (PEP-CK) was also measured. Experimental groups: 1, intact rats; 2, rats infused with somatostatin through the femoral vein; 3, bilateral adrenodemedullated (ADMX) rats; 4, somatostatin infused ADMX rats; 5, 5-methoxyindole-2-carboxylic acid (MICA) was injected intraperitoneally 30 minutes before injection of neostigmine into the third cerebral ventricle of intact rats. MICA treatment completely suppressed the increase in hepatic glucose in fasted rats, but had no effect in fed rats. Phosphorylase-a activity was not changed in fasted rats, but increased in fed rats, intact rats, somatostatin-infused rats, somatostatin-infused ADMX rats, and ADMX rats in that order. PEP-CK was not changed in fed rats, but increased at 60 and 120 minutes after neostigmine injection into the third cerebral ventricle in fasted rats. We conclude that, in fed states, brain cholinergic activation causes glycogenolysis by epinephrine, glucagon, and direct neural innervation. In fasted states, on the other hand, gluconeogenesis is dependent on epinephrine alone to increase hepatic glucose output.
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PMID:Central nervous system control of glycogenolysis and gluconeogenesis in fed and fasted rat liver. 257 6

The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output.
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PMID:Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats. 287 43

Acetylcholine, at concentrations of 10(-10)--10(-7) M, inhibited the release of immunoreactive somatostatin (SRIF) from rat hypothalamic segments which had been maintained in short term culture for 24 h. Neostigmine (10(-6) M), an anticholinesterase, also inhibited the release of SRIF, whereas atropine (10(-6) M), a muscarinic anticholinergic, had no effect on basal SRIF release but blocked the inhibition caused by acetylcholine (10(-8) M). However, hexamethonium (10(-6) M), a nicotinic antagonist, did not abolish the inhibition induced by acetylcholine. Potassium depolarization (56 mM KCl) caused stimulation of SRIF release, which was dependent on the presence of calcium in the incubation medium. SRIF was measured by a RIA sensitive to 1 pg/tube. Authenticity of immunoreactive SRIF released was suggested by immunological parallelism and chromatographic criteria using gel and high pressure liquid systems. These results suggest that muscarinic cholinergic mechanisms may have a regulatory role modulating the secretion of SRIF and, consequently, GH through actions at a hypothalamic level.
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PMID:Acetylcholine inhibits the release of somatostatin from rat hypothalamus in vitro. 610 1

This study evaluated the effect of stimulating the central nervous system (CNS) with neostigmine, an inhibitor of acetylcholinesterase, on the blood lactate concentration in fed rats and in rats fasted for 48 hours. After the rat was anesthetized with pentobarbital, neostigmine was stereotaxically injected into the third cerebral ventricle. In fed rats, the central injection of neostigmine significantly increased the blood lactate level, while concomitantly increasing plasma glucagon, epinephrine and norepinephrine concentrations. Constant infusion of somatostatin throughout the experiments, to inhibit glucagon secretion from the pancreas, did not affect alterations in blood lactate by central injection of neostigmine. In adreno-medullated rats, CNS-stimulation by neostigmine still increased plasma norepinephrine significantly, however, the alteration in blood lactate was only one-third of that in intact rats. Intraperitoneal propranolol, but not phentolamine, prevented the rise in lactate. Neostigmine increased lactate in fasted rats as well as in fed rats. We conclude that in anesthetized rats, stimulation of the CNS by neostigmine increases blood lactate mainly through circulating epinephrine and partially through circulating norepinephrine or direct sympathetic nervous stimulation; glucagon does not appear to be involved in the increase in blood lactate.
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PMID:CNS regulation of blood lactate concentration in anesthetized rats. 791 Jun 51