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)

Some peptides of the glucagon-secretin family were found to stimulate intracellular cyclic AMP accumulation in cultured bovine choroid plexus epithelial cells. Vasointestinal peptide and porcine intestinal peptide at concentrations of 30 and 300 nM, respectively, evoked 50-fold elevations of cyclic AMP; half-maximal responses were obtained with concentrations of 15 and 102 nM for the two peptides, respectively. Secretin and glucagon each produced 25- to 50-fold elevations of cyclic AMP at 330 microM, but showed no effect below 3 microM. Gastric inhibitory peptide and prealbumin had little or no response at any concentration tested. Experiments measuring the cellular cyclic AMP accumulation in response to pairs of peptides suggested that vasointestinal peptide, porcine intestinal peptide and secretin act through a common receptor. Studies with antagonists to isoproterenol and histamine indicated that this receptor is distinct from the beta-adrenergic and H2-histamine receptors known to exist on choroidal cells.
 ...
PMID:Vasoactive intestinal peptide stimulates cyclic AMP metabolism in choroid plexus epithelial cells. 302 76

We have compared the effects of the secretin family of peptides and their synthetic fragments on gastric emptying (GE) and small intestinal transit (SIT) using an unanesthetized rat model which simultaneously measures the GE and SIT of both solids and liquids. The meal consisting of 5% polyethylene glycol w/v, 5% Indian ink v/v and 20 non-digestible plastic beads was given intragastrically 10 minutes after the intraperitoneal injection of 0.5 ml of saline or peptides (2 and 5 micrograms/kg). Plasma secretin and the immunospecificity of secretin fragments were determined. In control rats, the t1/2 for the GE of both solids and liquids were 56 +/- 3.8 and 19 +/- 2.3 minutes, respectively. Liquids emptied faster than the solids and liquids travelled ahead of the solids in the intestine. Secretin (5 micrograms/kg) inhibited GE of both solids and liquids by 33-37%. Secretin delayed the SIT of the meal by approximately 35%. Fragments of secretin and of VIP had no effect on GE and SIT of both solids and liquids. The whole molecule of secretin was required to inhibit GE and to delay SIT of solids and liquids. Glucagon, PHI and growth hormone releasing factor (GHRF1-44) inhibited GE and SIT of both solids and liquids. For all peptides tested, the inhibition of SIT was proportional to the inhibition of GE suggesting that the prolongation of SIT was secondary to delayed GE. These observations indicate that the peptides of the secretin family inhibit GE and prolong SIT. Thus, the structural requirement required for the secretin family of peptides to effect their motor actions on the stomach is similar to that required for pancreatic enzyme secretion.
 ...
PMID:Effect of the secretin family of peptides on gastric emptying and small intestinal transit in rats. 304 99

In the fasting state the mean portal blood flow demonstrated by the pulsed Doppler system with the Octoson in liver cirrhosis (LC) patients (velocity (PV), 10.2 +/- 3.5 (mean +/- SD) cm/sec, 7.0 +/- 2.6 cm/sec/m2; flow (PF), 579 +/- 262 ml/min, 383 +/- 184 ml/min/m2 (n = 40)) was significantly lower than that in control subjects (PV, 21.2 +/- 5.2 cm/sec, 14.7 +/- 3.9 cm/sec/m2; PF, 966 +/- 344 ml/min, 667 +/- 220 ml/min/m2 (n = 40)). Food intake increased PV by 15% and PF by 15% in LC (n = 8) and increased PV by 56%, PF by 125% in controls (n = 8). Glucagon increased PV by 30% and PF by 52% in LC (n = 10) and increased PV by 50% and PF by 120% in controls (n = 8). Secretin increased PV by 44% and PF by 75% in LC (n = 9) and increased PV by 66% and PF by 142% in controls (n = 8). Vasopressin decreased PV by 42% and PF by 54% in LC (n = 9) and decreased PV by 48% and PF by 62% in controls (n = 8). Insulin, gastrin, and prostaglandin E1 had no effect in either group.
 ...
PMID:Effects of food intake and various extrinsic hormones on portal blood flow in patients with liver cirrhosis demonstrated by pulsed Doppler with the Octoson. 354 85

The concentrations and contents of vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) in the brain and of these peptides along with secretin and glucagon-like immunoreactivity (GLI) in the gut were compared in a group of 16 5-day fasted adult Sprague-Dawley rats with the corresponding peptides in a group of 16 nonfasted littermates. The mean weight of the fasted rats at the beginning of the study was 263 +/- 10 g (+/- SEM) and was 177 +/- 7 g before killing, for a net loss of 33% of initial body weight; the 16 fed rats increased their mean weight from 225 +/- 11 to 284 +/- 12 g, for a net gain of 12%. During the 5-day fast there was no change in the weight of the cortex, hypothalamus, or brain stem. However, the weight of tissues from the gut decreased to about half the weight of the corresponding tissues in the fed animals. There was no significant change in brain VIP or CCK. VIP content in the gut was unchanged. However, because of the decrease in organ weight, its concentration almost doubled. Secretin concentrations in the gut of fasted rats did not change significantly, but organ contents fell to about half. The gut content of GLI also fell by half or more. The concentrations of CCK in methanol extracts of the duodenum and jejunum remained relatively constant, but those in acid extracts fell by 40% in the fasted animals. This represents an approximately 70% decrease in organ content of CCK. These findings are interpretable as demonstrating that during a prolonged fast neuronal CCK and VIP are well conserved, but endocrine CCK, secretin, and GLI are markedly decreased because of loss of intestinal mucosa.
 ...
PMID:Brain/gut peptides in fed and fasted rats. 380

Glucagon secretion is stimulated by cholinergic activation, and it is known that the polypeptides VIP (vasoactive intestinal polypeptide) and GIP (gastric inhibitory polypeptide) both potentiate this cholinergically induced glucagon secretion. In this study, we investigated whether secretin, which shows structural similarities to both VIP and GIP, affects basal and cholinergically induced glucagon secretion in the mouse. Secretin was injected i.v. to mice at dose levels varying from 0.53 to 17 nmol kg-1, and plasma samples were taken at 2, 6 and 10 min following injection. It was found that secretin in this wide dose range did not affect basal glucagon concentrations. When the cholinergic agonist carbachol was injected i.v. at 0.16 mumol kg-1, plasma glucagon levels were elevated; at 2 min at 0.84 +/- 0.04 ng ml-1 compared to 0.31 +/- 0.02 ng ml-1 in controls (P less than 0.001). A combination of carbachol and secretin (4.25 nmol kg-1) enhanced plasma glucagon levels to 1.22 +/- 0.07 ng ml-1. Thus, secretin potentiated carbachol-induced glucagon secretion by 70% (P less than 0.001). Concomitantly, plasma glucose levels were elevated: 10.8 +/- 0.4 mmol l-1, compared to 9.2 +/- 0.4 mmol l-1 in controls (P less than 0.001). We conclude that secretin, while being without effect on basal glucagon secretion, markedly potentiates cholinergically induced glucagon secretion in the mouse, resulting in increased plasma glucose levels.
 ...
PMID:Secretin potentiates cholinergically induced glucagon secretion in the mouse. 381 83

Water and electrolyte flux in response to systemic administration of four different gastrointestinal hormones were studied in a human with a chronic Thiry-Vella ileal loop. Gastrin infusion with a pharmacological dose of 4 micrograms/kg-hr has no effect. Responses to glucagon were proportional to infused doses with directly increased absorption of water and electrolytes (except bicarbonate). However, when gastrin was infused simultaneously with glucagon, the enhanced absorption was inhibited. Secretin only transiently increased absorption of fluid and electrolytes. In contrast to its effects on jejunum, CCK increased both water and electrolyte absorption from the ileum.
 ...
PMID:Water and electrolyte absorption from a human Thiry-Vella ileal loop. Responses to systemic administration of gastrin, glucagon, secretin, and cholecystokinin. 396 99

Vasoactive intestinal peptide (VIP), originally isolated from hog small intestinal mucosa, has been shown to cause small intestinal secretion. More recently, this peptide has been identified in the plasma and tumors of patients with the so-called "pancreatic cholera" syndrome. In order to explore the possible role of VIP in the pathogenesis of this syndrome, we examined the effects of this peptide and other hormones on the cyclic AMP levels, adenylate cyclase activity, and ion transport in in vitro preparations of ileal mucosa. In rabbit ileal mucosa, VIP (20 mug/ml) caused a prompt fivefold increase in cyclic AMP level, whereas nine other hormones, which have been postulated to cause intestinal secretion, failed to exert such an effect. Pentagastrin and glucagon also failed to increase cyclic AMP levels in canine ileal mucosa. An increase in mucosal cyclic AMP levels was observed at a VIP concentration of 0.1 mug/ml and appeared to be nearly maximal at 2.0 mug/ml. VIP (100 mug/ml) stimulated adenylate cyclase activity in a membrane preparation from rabbit ileal mucosa. Secretin (6.0 x 10(-5) M) failed to do so. When added to the serosal side of isolated rabbit ileal mucosa clamped in an Ussing chamber, VIP (2 mug/ml) increased short-circuit current (SCC) and caused net secretion of both Cl and Na. Net Cl secretion exceeded net Na secretion. These effects of VIP on mucosal cyclic AMP metabolism and ion transport are similar to those observed with cholera enterotoxin and certain prostaglandins. VIP was also tested with normal human ileal mucosa. At a concentration of 2 mug/ml it caused a fivefold increase in cyclic AMP level and an increase in SCC of the same magnitude as that caused by 5 mM theophylline. Addition of a second 2-mug/ml dose of VIP and addition of theophylline after VIP produced no further change in SCC. We conclude the VIP stimulates adenylate cyclase and active ion secretion in both rabbit and human ileal mucosa. This may be related to the pathogenesis of diarrhea in patients with the pancreatic cholera syndrome.
 ...
PMID:Vasoactive intestinal peptide stimulation of adenylate cyclase and active electrolyte secretion in intestinal mucosa. 436 34

1. The role of extracellular and intracellular Ca(2+) in pancreatic enzyme secretion has been assessed by correlating the exchange of (45)Ca with amylase secretion in the isolated uncinate pancreas of baby rats.2. The rate coefficient of (45)Ca efflux from pre-loaded glands declined continually (indicating that (45)Ca is retained in several different pools) and probably reflects changes in the concentration of cytoplasmic free (45)Ca, which is determined by the rate at which (45)Ca is released from intracellular organelles into the cytoplasm.3. The rate coefficient of (45)Ca release was not influenced by extracellular Ca(2+) or Mg(2+) concentrations.4. Cholecystokinin-pancreozymin (CCK-PZ) and acetylcholine accelerated the release of both (45)Ca and amylase in a dose-dependent fashion, even when extracellular Ca(2+) was reduced to 0.1 mM, but did not affect the initial rate of (45)Ca uptake by the tissue.5. In Ca(2+)-free media (containing 0.5 mM-EGTA) basal amylase secretion slowly declined and stimulated secretion was virtually abolished, but the accelerated release of (45)Ca was maintained.6. These observations indicate that natural stimuli of pancreatic enzyme secretion alter (45)Ca distribution in the cell by a process which is independent of extracellular Ca(2+) and which is associated with amylase secretion provided that the plasma membrane has not been depleted of Ca(2+).7. Secretin, glucagon and insulin did not influence (45)Ca release. Secretin slightly increased amylase secretion, but this may have been a washout effect.8. Replacement of extracellular Na(+) by Li(+) increased the release of (45)Ca and amylase, but only in the presence of extracellular Ca(2+). Li(+)-substitution also increased (45)Ca uptake. Thus, under special conditions, secretion may be stimulated when increased amounts of Ca(2+) are made available from extracellular sources.9. Hyperosmolarity (known to increase (45)Ca release in muscle) also accelerated (45)Ca release and amylase secretion.10. 2,4-Dinitrophenol markedly accelerated (45)Ca efflux but did not stimulate amylase secretion, indicating that a rise in cytoplasmic Ca(2+) will not initiate secretion if energy metabolism is impaired.11. CCK-PZ slightly increased the rate coefficient of (42)K release, indicating a changed membrane permeability.12. The stimulatory effects of CCK-PZ and acetylcholine were suppressed during Na(+)-substitution by Li(+), suggesting that the Na(+) concentration gradient across the membrane is important in secretion.13. It is concluded that the primary action of CCK-PZ and acetylcholine may be to increase the influx of Na(+) into the cell by changing membrane permeability. This in turn is responsible for the release of Ca(2+) from intracellular stores (probably endoplasmic reticulum), leading to a rise in Ca(2+) concentration close to the structures involved in enzyme secretion. Secretion then follows provided that ATP is available and the plasma membrane is not depleted of Ca(2+).
 ...
PMID:The relationship between calcium exchange and enzyme secretion in the isolated rat pancreas. 477 43

The effects of VIP and related-peptides (PHI, secretin, glucagon) on cyclic AMP formation were investigated in intact pieces of rabbit retina. VIP and PHI increased cyclic AMP levels with EC50 of 160 nM and 300 nM respectively. At 5 microM the peptides increased cyclic AMP 46 fold (VIP) and 38 fold (PHI). Secretin was much less potent and glucagon was totally inactive. VIP was also tested for its effects on glycogen levels under similar experimental conditions. In contrast to its pronounced glycogenolytic action in mouse cerebral cortical slices, VIP at 1 microM decreased only moderately (38.3%) 3H-glycogen newly synthesized from 3H-glucose by pieces of rabbit retina. Furthermore a discrepancy between the efficacy of VIP in increasing cyclic AMP and in promoting glycogenolysis appears to exist. A similar dissociation between these two cellular events was also observed with other neuroactive substances. Thus the pronounced increase in cyclic AMP induced by dopamine and forskolin was accompanied by only a moderate decrease in 3H-glycogen levels. Conversely 50 mM potassium induced a 79.9% decrease in 3H-glycogen levels without any significant increase in cyclic AMP.
 ...
PMID:The effects of VIP on cyclic AMP and glycogen levels in vertebrate retina. 608 32

We have assessed the presence of VIP/PHI/secretin receptors in heart by: (1) testing the ability of the corresponding peptides to activate adenylate cyclase in cardiac membranes from rat, dog, Cynomolgus monkey and man, and (2) examining the ability of the same peptides to exert inotropic and chronotropic effects on heart preparations from rat and Cynomolgus monkey in vitro. Based on their affinity for natural peptides and synthetic analogs, two types of VIP/PHI/secretin receptors were characterized: the relatively nonspecific "secretin/VIP receptor" of rat heart (that is "secretin-preferring" only in that secretin was more efficient than VIP in stimulating adenylate cyclase), and the "VIP/PHI-preferring" receptor of man, monkey and dog heart. Four physiopathological situations affecting secretin/VIP receptors in rat heart were explored: In male rats from the Okamoto strain and the Lyon strain, two strains presenting spontaneous hypertension, heart membranes exhibited a markedly decreased response of adenylate cyclase to secretin/VIP, with lesser alterations in the responses to isoproterenol and glucagon. This impairment developed in parallel with the occurrence of hypertension and was reproduced in normotensive rats submitted to chronic isoproterenol treatment (but not in Goldblatt hypertensive rats). These findings are consistent with a hyperactivity of norepinephrine pathways in spontaneously hypertensive rats, leading to a reduced number of cardiac post-junctional secretin/VIP receptors bound to adenylate cyclase. Heart membranes from genetically obese (fa/fa) Zucker rats also exhibited severely decreased responses to secretin/VIP with lesser alterations in the responses to glucagon and isoproterenol. These anomalies were specific for the heart, and developed in concomitance with obesity. The first anomaly could not be corrected by severe food restriction. Secretin stimulation of heart adenylate cyclase was also selectively altered in streptozotocin-diabetic rats. Thus, two types of diabetic cardiomyopathy were characterized by a severe local alteration of secretin/VIP receptors coupled to adenylate cyclase. Hypothyroidism, provoked in rat by thyroidectomy or propylthiouracil treatment, again induced a marked decrease in secretin-stimulated cardiac adenylate cyclase activity. In rat papillary muscle electrically stimulated in vitro, secretin exerted a positive inotropic effect. This effect was reduced in obese (fa/fa) Zucker rats. In rat right atrium, secretin also exerted a positive chronotropic effects.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Heart receptors for VIP, PHI and secretin are able to activate adenylate cyclase and to mediate inotropic and chronotropic effects. Species variations and physiopathology. 608 34


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