Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptide YY (PYY) is a 36 amino acid peptide produced by mucosal endocrine cells of the ileum and colon which inhibits acid secretion and intestinal transit in man. To assess its effects on metabolites and digestive hormones PYY was infused into 18 fasting normal subjects at three dose levels (0.06, 0.19, and 0.57 pmol kg-1 min-1), each for a period of 1 h. During the infusions mean plasma PYY levels increased by 8, 25, and 73 pmol/liter, respectively. The mean disappearance half-time on stopping the infusions was 9.2 +/- 0.4 (SEM) min. The mean MCR was 7.3 +/- 0.7 ml kg-1 min-1 and the apparent volume of distribution was calculated to be 94 +/- 9 ml kg-1. During the highest dose infusion there was a significant increase in both systolic and diastolic blood pressure, of 8.6 +/- 3.7 mmHg (P less than 0.05) and 10.9 +/- 3.0 mmHg (P less than 0.01), respectively. PYY caused a significant 50% reduction in plasma pancreatic polypeptide concentrations (P less than 0.05) and a 55% reduction in circulating motilin levels (P less than 0.05). PYY had no significant effect on circulating concentrations of insulin, glucagon, gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, or vasoactive intestinal peptide. PYY also had no significant effect on circulating concentrations of glucose, lactate, glycerol, or nonesterified fatty acids. This recently discovered human intestinal hormonal peptide thus has significant effects both on gastrointestinal hormones (motilin and pancreatic polypeptide) and blood pressure in man, but appears not to influence glucose or lipid metabolism.
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PMID:Peptide YY kinetics and effects on blood pressure and circulating pancreatic and gastrointestinal hormones and metabolites in man. 375 28

Diminished concentrations of the gut neuropeptide, vasoactive intestinal peptide (VIP), have been measured by radioimmunoassay in man and mouse models of Hirschsprung's disease. This in vitro study was designed to ascertain the functional response to VIP in aganglionic colon. Seven piebald lethal (PLM) mice with histologically verified aganglionosis and seven normal littermates (NLM) were sacrificed. Distal colonic segments were placed in standard oxygenated tissue baths and responses to electrical field stimulation (EFS), acetylcholine (ACh), and VIP recorded and analyzed by a motility index (MI). Aganglionic colonic tissues from PLM exhibited marked basal contractile activity in contrast to NLM (MI = 19.5 +/- 2.0 SEM v 6.5 +/- 3.6 SEM, P less than .01). In NLM tissues, VIP reduced the MI to ACh challenge by 49% (P less than .01), while in PLM tissues, a nonsignificant 22% reduction was observed. VIP blocked the response to EFS in NLM tissues, while no response was elicited to EFS in PLM tissues. An in vitro deficit in the VIP inhibitory response to ACh challenge is apparent in PLM with distal colonic aganglionosis. The increased basal activity and reduction in responsiveness to VIP, observed in the PLM tissues, support a generalized reduction in the function of the inhibitory innervation of the aganglionic colon.
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PMID:Functional response to vasoactive intestinal peptide in piebald lethal mice. 379 77

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.
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PMID:Brain/gut peptides in fed and fasted rats. 380

Synthetic neurotensin was infused into five healthy subjects at a mean dose of 2.3 pmol/kg . min for 30 min, producing a rise in plasma neurotensin concentrations, measured by RIA of 104 +/- 10 (mean +/- SEM) pmol/liter. The mean disappearance half-time on stopping the infusion was 3.8 +/- 0.2 min. The MCR was 16 +/- 1 ml/kg . min, and the apparent space of distribution was 88 +/- 6 ml/kg. During the neurotensin infusions, plasma pancreatic polypeptide rose by 145 +/- 54 pmol/liter. In contrast to results in experimental animals, there was no significant change in the pulse or blood pressure of the subjects or any significant change in blood glucose or plasma concentrations of insulin, glucagon, gastric inhibitory peptide, gastrin, motilin, or vasoactive intestinal peptide. Similarly, there was no change in plasma concentrations of TSH, GH, PRL, LH, and FSH.
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PMID:Neurotensin infusion in man: pharmacokinetics and effect on gastrointestinal and pituitary hormones. 700 47

Gastric acid secretion and gastrointestinal hormone levels were measured in healthy non-diabetic subjects after metformin treatment (1.5 g/day). The maximum acid output was increased from 15.7 +/- 3.9 mmol/h (mean +/- SEM) to 30.0 +/- 7.1 mmol/h (p < 0.05) and the peak acid output was increased from 16.4 +/- 4.1 mmol/h to 31.7 +/- 7.2 mmol/h (p < 0.05) after two weeks treatment. Serum insulin, gastric inhibitory polypeptide and secretin levels were normal. After treatment for one week, however, there was a significant increase in fasting vasoactive intestinal peptide (VIP) from 83 +/- 6 ng/1 to 102 +/- 9 ng/1 (p < 0.02) and in stimulated VIP from 58 +/- 5 ng/1 to 79 +/- 5 ng/1 (p < 0.05). Stimulated glucagon-like immunoreactivity (GLI) was also increased from 82 +/- 10 ng/1 to 174 +/- 24 ng/1 (p < 0.01) after one week's treatment. It is suggested that metformin acts as a weak histamine agonist.
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PMID:The effect of metformin treatment on gastric acid secretion and gastrointestinal hormone levels in normal subjects. 741 69

Radioligand assays of the membrane fraction of hen hypothalamic tissues involving the preoptic (HPOA) or median eminence (HMEA) areas revealed the presence of a specific binding component to chicken vasoactive intestinal peptide (cVIP) having properties of a receptor. The equilibrium dissociation constant (Kd) was 0.70 +/- 0.07 nM (Mean +/- SEM; N = 5) in HPOA and 1.02 +/- 0.15 nM (N = 5) in HMEA as estimated by Scatchard analysis of saturation studies, and was 0.91 +/- 0.11 nM (N = 3) (HPOA) and 1.25 +/- 0.09 nM (N = 3) (HMEA) as determined by a kinetic analysis. The maximum binding capacity (Bmax) obtained by Scatchard analysis was 167 +/- 19 fmol/mg protein (N = 5) (HPOA) and 133 +/- 17 fmol/mg protein (N = 5) (HMEA). The Kd and Bmax values obtained by Scatchard analysis were similar in the two areas of the hypothalamus and in both laying and nonlaying hens. Administration of cVIP in vivo caused a decrease in specific cVIP binding. These results suggest the presence of a VIP receptor in the hen hypothalamus.
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PMID:Presence of vasoactive intestinal peptide receptor in the hen hypothalamus. 762 62

The purpose of this study was to determine whether encapsulation of vasoactive intestinal peptide (VIP) into liposomes potentiated its vasorelaxant effects in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (53 +/- 1 microns) in the hamster cheek pouch before, during and after suffusion of VIP, liposomes and VIP encapsulated into liposomes for 7 min. We found that VIP (0.05, 0.1 & 1.0 nmol) induced significant, time- and concentration-dependent vasodilation (9 +/- 1%, 13 +/- 3% and 14 +/- 1% increase from baseline values, respectively; mean +/- SEM; n = 12; p < 0.05). Arteriolar diameter returned to baseline values within 1-4 min after suffusion was stopped. These effects were significantly potentiated when VIP (0.05, 0.1 & 1.0 nmol) was encapsulated into liposomes (26 +/- 6%, 38 +/- 7% and 34 +/- 3% increase from baseline values, respectively; n = 12; p < 0.05). In addition, arteriolar diameter returned to baseline values 5-13 min after suffusion was stopped. Suffusion of liposomes alone had no significant effects on arteriolar diameter (n = 12; p > 0.5). We conclude that encapsulation of VIP into liposomes potentiates and prolongs of its vasorelaxant effects in the peripheral microcirculation in vivo.
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PMID:Encapsulation of vasoactive intestinal peptide into liposomes: effects on vasodilation in vivo. 767 36

The possibility that pituitary adenylyl cyclase-activating peptide (PACAP) is an inhibitory neurotransmitter has been investigated in the taenia of the guinea-pig caecum. The action of PACAP on muscle contractility and its ability to alter levels of adenosine-3':5'-cyclic monophosphate (cyclic AMP) and guanosine-3':5'-cyclic monophosphate (cyclic GMP) were investigated. PACAP-1-27 was an effective agonist, giving relaxations comparable in magnitude to isoproterenol; its EC50 was 3.4 x 10(-7) M. PACAP (10(-6) M) caused an almost two-fold increase in cyclic AMP levels; but the level of cyclic GMP was not affected. The relaxation caused by PACAP was slow in onset, with a latency of 5.8 +/- 0.8 s and reached a maximum at 9.1 +/- 1.1 s after onset. The relaxation was significantly reduced by apamin (10(-6) M) and suramin (10(-4) M) but was not reduced by tetrodotoxin (10(-7) M). Relaxation of the taenia coli caused by electrical stimulation of the inhibitory nerves was greatly reduced by apamin but only slightly reduced by suramin. PACAP-like immunoreactivity (-IR) was localised immunohistochemically in varicose nerve fibres within the taenia coli and in the underlying myenteric plexus and circular muscle. Approx. 50% of vasoactive intestinal peptide (VIP)-IR nerve fibres in the taenia also had immunoreactivity for PACAP; conversely, almost all PACAP-IR fibres were immunoreactive for VIP. PACAP-IR and substance P (SP)-IR were generally in separate fibres; only about 5% of SP-IR fibres were PACAP-IR. Radioimmunoassay revealed tissue concentrations of PACAP-1-27 and PACAP-1-38 of 1.0 +/- 0.1 and 2.1 +/- 0.3 (SEM) pmol/g wet weight of tissue, respectively. Material with PACAP-1-27 immunoreactivity co-eluted with authentic PACAP-1-27 on gel filtration chromatography, and PACAP-1-38 immunoreactivity also co-eluted with the authentic peptide. This study provides structural, chemical and pharmacological evidence that PACAP could be involved in inhibitory neurotransmission to the taenia coli of the guinea-pig caecum.
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PMID:Histochemical, pharmacological, biochemical and chromatographic evidence that pituitary adenylyl cyclase activating peptide is involved in inhibitory neurotransmission in the taenia of the guinea-pig caecum. 771 25

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) is a neuropeptide related to vasoactive intestinal peptide-secretin-glucagon which stimulates adenylate cyclase in cultured rat pituitary cells and stimulates LH and FSH release in vitro and in vivo. Because the cAMP-protein kinase-A pathway regulates the gonadotropin subunit messenger RNAs (mRNAs) and modulates GnRH-stimulated gonadotropin secretion in vitro, we examined the effects of PACAP38 on gonadotropin secretion and subunit mRNA levels. Anterior pituitary cells were prepared from 7-week-old male rats castrated at 5 weeks of age. In monolayer cultures stimulated with GnRH, 0.1-10 nM PACAP38 decreased (P < 0.05) the EC50 for GnRH dose-dependently without affecting the maximum LH secretory response. Cells were next stimulated with 1-min pulses of 2.5 nM GnRH every hour for 9 h in the absence or presence of 10 nM PACAP38, which was perifused continuously. The amplitude of GnRH-induced LH, FSH, and alpha-subunit secretory episodes from PACAP38-treated cells rose (P < 0.01) gradually to 233 +/- 54%, 197 +/- 44%, and 378 +/- 104%, respectively (mean +/- SEM; n = 5 experiments), of the value for control cells lacking PACAP38. This enhancement was sustained for at least 3 h after PACAP38 was removed from the perifusion medium. With PACAP treatment, interpulse secretion of LH and alpha-subunit increased gradually (P < 0.01) to 174 +/- 21% and 212 +/- 64% of the value for chambers stimulated with GnRH alone (control), respectively, whereas interpulse secretion of FSH declined (P < 0.001) to 75 +/- 7% of the control value. In contrast to the gradual effect of PACAP38 to enhance GnRH-induced hormone secretion, PACAP38 alone produced a transient burst of gonadotropin secretion. At the completion of the perifusions, total RNA was extracted and gonadotropin subunit mRNA levels were determined by Northern analysis. GnRH increased (P < 0.01) FSH beta mRNA to 438 +/- 52% of the level in cells stimulated with medium alone (control). Adding PACAP38 to the perifusion medium partially blocked (P < 0.01) the effect of GnRH (178 +/- 20% of the control value), and PACAP38 alone reduced (P < 0.01) FSH beta mRNA levels to 31 +/- 3% of the control value. By contrast, alpha-subunit mRNA levels were increased by both PACAP38 (143 +/- 4% of the control value; P < 0.01) and GnRH (121 +/- 2% of the control value; P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of pituitary adenylate cyclase-activating polypeptide on gonadotropin secretion and subunit messenger ribonucleic acids in perifused rat pituitary cells. 791 30

In an attempt to establish the possible role of vasoactive intestinal peptide (VIP) in the regulation of vasomotor tone of coronary artery bypass grafts, this study examined the action of this peptide and the distribution of [125I]VIP binding sites in isolated human gastroepiploic artery (GEA), internal mammary artery (IMA) and saphenous vein. VIP (10(-10)-3 x 10(-7) M) elicited concentration-dependent relaxations in ring segments that were preconstricted with the thromboxane analog U46619. The maximal response was mean +/- SEM 79 +/- 4%, 52 +/- 8% and 23 +/- 3% of glyceryl trinitrate (3 x 10(-5) M)-induced maximal smooth muscle relaxation in the GEA, IMA and saphenous vein, respectively. Both receptor-binding and competition studies indicated that there was a higher density of [125I]VIP binding to smooth muscle cells of the GEA and IMA than to the saphenous vein. Total binding, at 50pM [125I]VIP, was 604 +/- 89, 381 +/- 64 and 87 +/- 12 amol/mg wet weight in the GEA, IMA and saphenous vein, respectively. Dense binding of [125I]VIP was associated with the tunica media in all the vessels studied. There was also binding to perivascular regions with no obvious binding to endothelial cells. These data demonstrate that arterial grafts, particularly the GEA, are more sensitive to the relaxant effect of VIP and this may possibly be due to a higher receptor density.
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PMID:Action of vasoactive intestinal peptide and distribution of its binding sites in vessels used for coronary artery bypass grafts. 838 26


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