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

We previously demonstrated that treatment with indomethacin in vivo significantly blunted the glucagon-induced glycemic response in the rat. This prostaglandin synthetase (cyclo-oxygenase) inhibitor also accentuated the evanescent effect of glucagon on hepatic glucose output in the intact, anesthetized rat. In this report, we present evidence that impairment of glucagon action in the rat liver by indomethacin is mediated through its inhibitory effect on both cAMP-dependent and cAMP-independent hepatic protein kinase. Indomethacin treatment did not have a measurable effect on any of the other components of the glucagon transducer system. Furthermore, infusion with glucagon for two hours that maintained plasma glucagon values at high physiological levels significantly reduced hepatic cAMP-dependent protein kinase activity without altering its Km. Glucagon infusion also down-regulated its own hepatic receptors and glucagon-stimulated cAMP production; prostaglandin E1-stimulated cAMP production was not affected. We concluded that prostaglandins may play a role in the regulation of hepatic protein kinases involved in the glucagon-stimulated glycogenolytic response and that glucagon-induced down-regulation extends at least to the hepatic protein kinases. However, a direct effect of indomethacin or protein kinase and the adenylate cyclase complex cannot be ruled out.
 ...
PMID:Modulation of hepatic protein kinase activity by indomethacin. 608 43

Bombesin was injected into the cerebral ventricle of male rats anesthetized with urethane to study its effect on plasma levels of immunoreactive somatostatin (IRS) in hypophysial portal and jugular blood. An intraventricular injection of bombesin (0.2 and 2 micrograms/rat) caused a significant and dose-related increase in plasma IRS in hypophysial portal blood but not in jugular blood. Although bombesin placed into the cerebral ventricle is known to stimulate glucagon and epinephrine release, an iv injection of glucagon (100 micrograms/100 g BW) or epinephrine (2.5 micrograms/100 g BW) did not cause any significant changes in plasma IRS levels in hypophysial portal and jugular blood, suggesting that these substances do not mediate bombesin stimulation of portal IRS release. Pretreatment with naloxone (75 micrograms/100 g BW, iv) failed to affect the portal IRS release induced by bombesin (2 micrograms/rat), indicating that the opiate receptor is not likely to be involved in this reaction. To ascertain whether IRS released by bombesin into hypophysial portal blood is biologically active, the effect of bombesin on the plasma GH level was then examined. Bombesin (2 micrograms/rat) injected intraventricularly completely suppressed the rise of plasma GH after the intraventricular injection of beta-endorphin (1 microgram/rat) or the iv injection of prostaglandin E1 (5 micrograms/100 g BW). Bombesin thus appears to stimulate the secretion of IRS, and probably biologically active somatostatin as well, from the hypothalamus into hypophysial portal blood, thereby inhibiting GH release from the anterior pituitary.
 ...
PMID:Stimulation by bombesin of immunoreactive somatostatin release into rat hypophysial portal blood. 611 30

Using a new model of a reversible pancreatic fistula which allows the long-term-investigation under nearly physiological conditions on the unrestrained dog, we tested the effect of somatostatin (50 micrograms), calcitonin (4 micrograms), glucagon (1 microgram), and prostaglandin E1 (150 micrograms) on the exocrine pancreatic function in 45 experiments over a period of 13 h: SST inhibits the basal as well as the secretin or CCK-stimulated secretion: calcitonin shows inhibition of the stimulated secretion only; glucagon blocks the secretin-stimulated pancreatic function; and PGE1 reduces the bicarbonate concentration and trypsin output in secretin stimulation, but in one of the two series it stimulates the basal secretion.
 ...
PMID:The effect of SST, glucagon, calcitonin and PGE1 on exocrine pancreatic secretion in the unrestrained dog in long-term experiments. 611 65

The effects of PGE1, PGE2 and PGD2 on somatostatin, insulin and glucagon secretions were investigated at various glucose concentrations using the isolated perfused rat pancreas. At glucose concentrations varying from 0 to 16.7 mM, PGE1 and PGE2 enhanced somatostatin release in a glucose dose-dependent manner. PGE1 did not significantly stimulate insulin secretion at glucose concentrations of 4.4 mM or less, but did at glucose concentrations of 8.8 mM or more, PGE2 augmented insulin release at 4.4 and 16.7 mM glucose, but not in the absence of glucose. Glucagon release was induced by PGE1 and PGE2 in a biphasic pattern with the maximal response in the absence of glucose. Like PGE1 and PGE2, PGD2 stimulated insulin and glucagon release in a glucose-related fashion. PGD2, however, was not capable of stimulating somatostatin release at various glucose concentrations even in the presence of 16.7 mM glucose. In conclusion, PGE1, PGE2, and PGD2 increase insulin and glucagon secretion in a glucose-dependent manner. PGE1 and PGE2 also stimulate somatostatin release, but PGD2 has no effect on somatostatin secretion at the doses studied.
 ...
PMID:Different effects of prostaglandin E1, E2 and D2 on pancreatic somatostatin release. 615 34

Prostaglandin E1 (PGE1), a component in the hormone-supplemented, serum-free medium for the Madin Darby canine kidney (MDCK) cell line, has been proposed to increase MDCK cell growth by increasing intracellular cyclic AMP levels. The association between increased intracellular cyclic AMP and the growth stimulatory effect of PGE1 has been examined in normal MDCK cells and in PGE1-independent variants of MDCK. These variant cells have lost the PGE1 requirement for long term growth in defined medium. Normal MDCK cells had almost twofold higher intracellular cyclic AMP levels during growth in Medium K-1 (9.0 pmol/mg protein) than in Medium K-1 minus PGE1. Furthermore, PGE1-independent clone 1 had higher intracellular cyclic AMP levels in Medium K-1 minus PGE1 than normal MDCK cells in Medium K-1. This latter observation suggests that the PGE1 requirement for MDCK cell growth is associated with the low intracellular cyclic AMP levels of this cell line. An involvement of cyclic AMP in the growth response to PGE1 is supported by these observations, as well as by the growth stimulatory effects of other agents that affect cyclic AMP metabolism in MDCK cells. These agents include glucagon, isobutyl methylxanthine (IBMX), and dibutyryl cyclic AMP. The growth of PGE1-independent clone 1 was inhibited rather than stimulated by PGE1. Similarly, PGE1-independent cell growth was inhibited by IBMX and dibutyryl cyclic AMP. However, the growth response to one agent which increases cyclic AMP (glucagon) was retained in PGE1-independent clone 1. This result suggests that the effect of glucagon is not associated with increases in intracellular cyclic AMP. The growth stimulatory effect of epidermal growth factor (EGF) on normal MDCK cells was also studied. Although EGF does not act via a cyclic AMP-mediated mechanism, EGF increased normal MDCK cell growth and substituted for PGE1 in Medium K-1. Thus, EGF and PGE1 could possibly affect similar growth-related functions in MDCK cells, although by different pathways. This possibility was examined further, using PGE1-independent clone 1. EGF, like glucagon, was still growth stimulatory to the PGE1-independent cells. Consequently, the biochemical pathways by which EGF and PGE1 increase MDCK cell growth probably do not converge.
 ...
PMID:PGE1-independent MDCK cells have elevated intracellular cyclic AMP but retain the growth stimulatory effects of glucagon and epidermal growth factor in serum-free medium. 620 19

Binding of 125I-labeled vasoactive intestinal peptide (VIP) to dispersed enterocytes prepared from guinea pig small intestine was saturable, temperature dependent, and reversible, and reflected interaction of the labeled peptide with a single class of binding sites. Each enterocyte possessed approximately 60,000 binding sites and binding of the tracer to these sites could be inhibited by VIP [concentration for half-maximal effect (Kd), 12 nM] and by secretin (Kd greater than 1 micro M), but not by glucagon, gastrin, cholecystokinin, calcitonin, bombesin, litorin, physalaemin, substance P, eledoisin, serotonin, carbamylcholine, or histamine. With VIP and secretin, there was a close correlation between the relative potency for inhibition of binding of 125I-VIP and that for increasing cellular cAMP. For a given peptide, however, a 10-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of cellular cAMP. In addition to inhibiting binding of 125I-VIP and increasing cellular cAMP in enterocytes, secretin caused an increase in short-circuit current across guinea pig small intestine in vitro. Prostaglandin E1 increased cellular cAMP, but did not alter binding of 125I-VIP and the increase in cAMP caused by prostaglandin E1 plus VIP or secretin was equal to the sum of the increase caused by each agent alone.
 ...
PMID:Receptors for vasoactive intestinal peptide and secretin on small intestinal epithelial cells. 624 88

Cyclic AMP levels in liver slices of hamsters exposed to 35 degrees C for 21 days and controls maintained at 22 degrees C was found to be similar in basal conditions. Glucagon (10 microgram/ml) caused 3.5 times elevation of cyclic AMP levels in control hamsters and 9 times elevation in 35 degrees C exposed hamsters, thus a difference of 150% of the nucleotide concentration was found between the two experimental groups. When 10(-2)M theophylline was added, the cyclic AMP levels were 80% higher in 35 degrees C exposed hamsters both in the presence and absence of 10 microgram/ml glucagon. The difference between controls and heat exposed animals was found to be the same when various concentrations of both glucagon or prostaglandin E1 were added to the liver slices. Adenylate cyclase activity was similar in both experimental groups, while low Km phosphodiesterase was significantly less active in the liver of 35 degrees C exposed animals when compared to the controls.
 ...
PMID:The effect of glucagon and prostaglandin E1 on cyclic AMP levels in liver of heat exposed hamsters. 624 68

Adenylate cyclase responses to pituitary hormones including adrenocorticotropic hormone (ACTH), biogenetic amines, prostaglandin E1 (PGE1), angiotensin II, and glucagon were evaluated in adrenocortical tumors and hyperplastic adrenal tissues, obtained from patients with Cushing's syndrome at surgery, and in normal adrenals. The adenylate cyclase of two normal adrenals was activated only by ACTH and PGE1 among the hormones tested, while that of two hyperplastic adrenal tissues due to excessive pituitary ACTH secretion was stimulated only by ACTH. Of five ACTH-responsive adrenocortical adenomas, in contrast, three were stimulated by norepinephrine, two by epinephrine, one by thyroid-stimulating hormone, and one by luteinizing hormone in addition to ACTH, indicating the presence of multiple receptors for hormones other than ACTH and PGE1 in these four tumors. The cyclase of an ACTH-unresponsive adrenocortical carcinoma ws activated only by PGE1 and not by other hormones including ACTH, whereas that of an ACTH-responsive adrenocortical nodular hyperplasia was stimulated by ACTH and glucagon but not by other hormones including PGE1. These results indicate the presence of multiple receptors for hormones other than ACTH and PGE1, the normal adrenocortical stimulants, in human adrenocortical tumors, particularly in adrenal adenomas, but not in normal and hyperplastic (of whichever an etiology) adrenocortical tissues, suggesting a functional alteration of the cellular membrane receptors in human adrenocortical tumors.
 ...
PMID:Multiple hormone receptors in the adenylate cyclase of human adrenocortical tumors. 625 40

Several prostaglandins were found to inhibit hormone-induced cyclic AMP accumulation in suspensions of intact rat hepatocytes. Prostaglandin E1 in concentrations of 0.05--25 micrometers inhibited the cyclic AMP response to glucagon. Maximal inhibition was about 50%. The effect was rapid, being evident within 30 s. Prostaglandins E2, F1 alpha, F2 alpha, A1 and A2 also inhibited the glucagon effect on cyclic AMP in hepatocytes. In cells made highly responsive to adrenaline, by pretreatment of the animals with the carcinogen 2-acetylaminofluorene, and inhibitory effect of prostaglandin E1 was seen also on adrenaline-induced cyclic AMP accumulation. The mechanism of the inhibitory effect of prostaglandins on hormone-stimulated cyclic AMP accumulation was not clarified. Prostaglandin E1 did not inhibit glucagon binding to intact hepatocytes, and so far we have not been able to demonstrate any effect of the prostaglandins on the adenylate cyclase or phosphodiesterase in broken cell preparations. It is concluded that while several previous studies have shown that stimulatory effects of prostaglandins on cyclic AMP are only marginal or lacking in parenchymal liver cells the present data indicate that several prostaglandins exert strong inhibitory interference with hormone-induced cyclic AMP accumulation.
 ...
PMID:Inhibitory effect of prostaglandins on the stimulation by glucagon and adrenaline of formation of cyclic AMP in rat hepatocytes. 626 9

A kidney cell line (MDCK) retains an adenylate cyclase system sensitive to glucagon, vasopressin, isoproterenol and prostaglandin E1. The stimulatory effect of glucagon on cAMP production was selectively lost in a cloned line derived from MDCK cells transformed by Harvey murine sarcoma virus. Sensitivity to glucagon was largely restored by treatment of the transformed cells with prostaglandin E1 or butyrate. Loss and reappearance of glucagon receptors seemed to be responsible for the observation. The parental MDCK line produced prostaglandins and in the transformed line, this function was abolished. These observations suggest that synthesis of glucagon receptors is controlled by endogenously produced prostaglandin in MDCK cells and that loss of glucagon receptors and their responsiveness in the transformed cells occurs as a consequence of the inability of these cells to synthesize this prostaglandin.
 ...
PMID:Loss and restoration of glucagon receptors and responsiveness in a transformed kidney cell line. 629 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>