Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bile flow rates and composition are subject to a wide variety of neural, endocrine and paracrine influences. The effects of these multiple factors may be different in the diseased liver compared to the response produced in the normal liver. As prostanoids may have a therapeutic role in liver disease it was intended to evaluate the effects of two principal therapeutic prostanoids, prostaglandin E2 and prostacyclin, on bile flow in dogs with a normal liver and in dogs with hepatotoxin-induced liver injury. Initially, in awake animals with chronic biliary and gastric fistulas the bile flow response to prostaglandin E2 and prostacyclin was evaluated and compared to the response produced by bile salt infusion alone and to that produced by the standard choleretic hormones, secretin and glucagon. The animals were then fed alpha-naphthylisothiocyanate (ANIT) and the studies repeated. ANIT is a hepatoxin that produces bile duct cell hyperplasia which was confirmed in dogs by demonstrating that ANIT increased [3H]thymidine incorporation by isolated canine bile duct cells. In normal dogs, the prostanoids, secretin, and glucagon increased hepatic bile flow. 10 days of ANIT feeding produced a hypercholeresis. While secretin was able to stimulate the hyperplastic biliary epithelium and increase bile flow over values produced by the hyperplastic biliary epithelium alone, neither prostaglandin E2, prostacyclin, or glucagon appeared to stimulate the hyperplastic biliary epithelium. As ANIT produced evidence of cholestasis and hepatocellular damage, only secretin would seem to have a potential therapeutic role in increasing bile flow in cholestatic liver disorders associated with bile duct cell hyperplasia.
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PMID:The effect of prostanoids on hepatic bile flow in dogs with normal liver and bile duct cell hyperplasia. 880 23

We have examined the binding of radio-iodinated vasoactive intestinal peptide (VIP) to rat platelets. The binding was time- and temperature-dependent and was reversible, saturable and specific. Scatchard analysis of binding data suggested the presence of a single class of binding sites, with Kd = 2.49 +/- 0.76 nM and Bmax = 112.1 +/- 54.6 fmol/10(8) cells. Several VIP-related peptides inhibited 125I-VIP binding to rat platelets with the following order of potency: helodermin > or = VIP > peptide histidine isoleucine. Glucagon, secretin, growth hormone-releasing hormone (GHRH), and gastric inhibitory peptide (GIP) were ineffective. VIP and the other peptides increased cyclic AMP production with the same order of potency as the inhibition of binding, but the stimulation by VIP was less marked than that by prostacyclin (PGI2). We conclude that rat platelets have functional, adenylate cyclase-linked, receptors that bind preferentially to helodermin and VIP.
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PMID:Characterization of VIP-and helodermin-preferring receptors on rat platelets. 883 17

Splanchnic and systemic arteriolar vasodilation plays an important role in ascites formation in cirrhosis. Octreotide produces splanchnic vasoconstriction, but the effects on systemic hemodynamics and renal function are controversial. This study evaluated the effect of subcutaneous octreotide administration on systemic hemodynamics, endogenous vasoactive systems, and renal function in cirrhotic patients with ascites. Twenty patients were included: 10 received octreotide 250 microg/12 hr subcutaneously (for five days), and 10 did not. No statistically significant changes were found in mean arterial pressure and cardiac rate. Octreotide induced a statistically significant decrease in plasma renin activity (P < 0.01), plasma aldosterone (P = 0.01) and plasma glucagon (P < 0.05). No significant variations were observed in other systemic vasoactive substances (nitric oxide and prostacyclin). Renal function was not modified in either group. In conclusion, in cirrhotic patients with ascites, subcutaneous octreotide administration decreases plasma glucagon, renin activity, and aldosterone without changing in systemic hemodynamics or renal function.
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PMID:Effect of subcutaneous administration of octreotide on endogenous vasoactive systems and renal function in cirrhotic patients with ascites. 979 Apr 52

Nitric oxide, prostacyclin, and glucagon have been implicated in promoting the hyperdynamic circulatory state of portal hypertension. Recent evidence also indicates that increased tumor necrosis factor-alpha (TNF-alpha) production is involved in the pathogenesis of this hemodynamic abnormality. This study was aimed at investigating in rats with portal vein stenosis (PVS) the effects on splanchnic hemodynamics of blocking circulating TNF-alpha and the factors mediating the vascular action of this cytokine in this setting. Anti-TNF-alpha polyclonal antibodies or placebo was injected into rats (n = 96) before and 4 days after PVS (short-term inhibition) and at 24 h and 4, 7, 10 days after PVS (long-term inhibition). Short-term TNF-alpha inhibition reduced portal venous inflow and cardiac index and increased splanchnic and systemic resistance. Portal pressure was unchanged, but portal-systemic shunting was decreased. After long-term TNF-alpha inhibition, portal venous inflow and portal pressure were unchanged, but arterial pressure and systemic resistance rose significantly. Anti-TNF-alpha PVS rats exhibited lower increments of systemic resistance after Nomega-nitro-L-arginine methyl ester and indomethacin administration and lower serum levels of TNF-alpha, nitrates-nitrites, and 6-keto-PGF1alpha, both over the short and the long term. Serum glucagon levels rose after long-term inhibition. In conclusion, the specific role played by TNF-alpha in the development of the hyperdynamic state of portal hypertension appears to be mainly mediated through an increased release of nitric oxide and prostacyclin. Maintenance of the splanchnic hyperemia after long-term TNF-alpha inhibition could be due to a compensatory release of glucagon.
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PMID:Factors mediating the hemodynamic effects of tumor necrosis factor-alpha in portal hypertensive rats. 1007 45

In liver cirrhosis, portal hypertension is a consequence of enhanced intrahepatic vascular resistance and portal blood flow. Significant vasodilation in the arterial splanchnic district is crucial for an increase in portal flow. In this pathological condition, increased levels of circulating endogenous vasodilators, including nitric oxide, prostacyclin, carbon monoxide, epoxyeicosatrienoic acids, glucagon, endogenous cannabinoids, and adrenomedullin, and a decreased vascular response to vasoconstrictors are the main mechanisms underlying splanchnic vasodilation. In this review, the molecular pathways leading to splanchnic vasodilation will be discussed in detail.
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PMID:Molecular Mechanisms Leading to Splanchnic Vasodilation in Liver Cirrhosis. 2840 77


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