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)

The local production of autocrine or paracrine agents in endocrine tissues represents an important level of hormonal regulation. The synthesis of neuropeptide-Y (NPY), substance-P (SP), and vasoactive intestinal peptide (VIP) in the rat anterior pituitary gland has been well demonstrated. We have now studied their expression in human postmortem pituitary tissue. Northern blot analysis of poly(A)+ RNA from whole human pituitaries revealed mRNA encoding the precursors for NPY, SP, and VIP whose hybridization characteristics were indistinguishable from those of the same mRNAs described in previously characterized human tissues. VIP mRNA was detectable in all samples tested, with NPY and preprotachykinin-A mRNA (which encodes SP) detectable in a subset of the pituitaries. The concentration of immunoreactive NPY in whole human pituitary was 3.8 +/- 1.1 pmol/g wet wt in males and 2.9 +/- 0.5 pmol/g wet wt in females (mean +/- SEM; n = 10), that of SP was 3.1 +/- 0.4 pmol/g wet wt in males and 5.2 +/- 1.3 pmol/g wet wt in females (n = 10), and that of VIP was 8.1 +/- 2.9 pmol/g wet wt in males and 5.3 +/- 1.6 pmol/g wet wt in females (n = 10). Size-fractionation of pituitary extracts by gel permeation chromatography revealed single peaks of NPY and VIP-like immunoreactivity in the positions of the standards, while SP-like immunoreactivity mostly eluted in the position of synthetic SP, with two minor immunoreactive peaks eluting earlier. The low levels of NPY, SP, and VIP and their mRNAs in the human pituitary are consistent with peptides having an autocrine/paracrine, rather than endocrine, mode of action.
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PMID:Expression of messenger ribonucleic acids encoding neuropeptide-Y, substance-P, and vasoactive intestinal polypeptide in human pituitary. 138 56

The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.
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PMID:Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise. 139 15

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel peptide of hypothalamic origin which increases adenylate cyclase activity in rat anterior pituitary cell cultures. The 38-amino acid peptide shows a close sequence homology to vasoactive intestinal peptide (VIP). Binding sites for PACAP in membranes from postmortem human brain tissue were studied using [125I]PACAP27 as the radioligand. High specific binding sites (amount of specific binding measured at 0.25 nM [125I]PACAP27 in femtomoles per mg protein +/- SEM; n = 4) were present in hypothalamus (344.5 +/- 13.0), brain stem (343.0 +/- 29.3), cerebellum (292.0 +/- 21.1), cortex (259.6 +/- 19.8), and basal ganglia (259.2 +/- 50.3). Specific binding sites in pituitary, although present, were less abundant (35.0 +/- 8.9). Binding of [125I]PACAP27 was reversible and time, pH, and temperature dependent. Despite the homology with VIP, VIP was a poor inhibitor of [125I]PACAP27 binding (IC50, greater than 1 microM) compared with PACAP27 (IC50, 0.5-1.3 nM) and PACAP38 (IC50, 0.2-1.3 nM). Scatchard plots of [125I]PACAP27 binding showed the presence of both high and lower affinity sites. Chemical cross-linking of PACAP-binding sites revealed that [125I]PACAP27 was bound to polypeptide chains of 67,000 and 48,000 mol wt. Thus, we have demonstrated the presence of PACAP-specific receptors in human brain which are not VIP receptors. This opens the possibility of PACAP functioning as a novel neurotransmitter/neuromodulator in human brain.
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PMID:Investigation and characterization of receptors for pituitary adenylate cyclase-activating polypeptide in human brain by radioligand binding and chemical cross-linking. 167 86

The present study was designed to investigate whether the vasoactive intestinal peptide (VIP) concentration in hypothalamic nuclei, dorsal raphe nucleus (DR) and pituitary lobes of lactating rats changes in physiological situations when prolactin (PRL) secretion is stimulated (suckling) or inhibited (pup separation). In addition VIP levels in blood plasma were determined in both situations. Acute suckling induced changes in VIP concentration only in the rostral part of the anterior hypothalamic (rAHN) and the paraventricular (PVN) nuclei of all the brain areas examined. VIP concentration in the rAHN increased at 5 min from 3.52 +/- 0.30 (mean +/- SEM) to 8.67 +/- 1.91 ng/mg protein (p less than 0.05) but fell to baseline values after 30 min suckling (p less than 0.05; 5 vs. 30 min). Although changes in VIP concentration in the suprachiasmatic nucleus (SCN) did not attain statistical significance, they followed the same trends as the changes of VIP in the rAHN. The opposite pattern of changes was observed in the PVN with a decrease in VIP concentration following 5 min suckling (p less than 0.01). At 30 min the VIP values showed a trend towards 0-min values. Pup removal did not affect VIP concentrations in the rAHN, PVN, SCN, median eminence, supraoptic nucleus and DR. VIP values were not detectable in the arcuate nucleus in any of the experimental situations examined. Lactation increased VIP concentration only in the rAHN and PVN when lactating rats with their pups were compared with virgin female diestrous rats. VIP concentration in the anterior lobe of the pituitary from lactating rats did not change with pup separation or suckling.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suckling-induced changes of vasoactive intestinal peptide concentrations in hypothalamic areas implicated in the control of prolactin release. 192 80

To investigate whether peptide YY (PYY) has a role in minimising fluid loss during diarrhoea, its effect on hypersecretion induced by vasoactive intestinal peptide (VIP) was studied in seven subjects with ileostomies. An isotonic electrolyte solution containing polyethylene glycol 4000 was infused directly into the duodenum and the effluent was collected for 40 min (baseline), then VIP was infused intravenously at 5 pmol.kg-1.min-1 for 500 min. PYY was infused intravenously at low doses (0.4 and 0.2 pmol.kg-1.min-1) for 100 min each during the continuous VIP infusion. Small-intestinal secretion was assessed by effluent weight and by polyethylene glycol dilution, which gave similar results. Plateau ileal output was 501 (SEM 33) ml/h during VIP infusion. PYY caused significant falls in secretion--to 404 (48) ml/h for the lower dose and to 323 (75) ml/h for the higher. It also prolonged small-bowel transit. These findings suggest that PYY is a natural inhibitor of diarrhoea and that its therapeutic potential merits investigation.
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PMID:Preliminary report: role of peptide YY in defence against diarrhoea. 197 88

The effect on heart rate of close i.a. injection of neurotensin (NT), substance P (SP), and vasoactive intestinal peptide (VIP) into the decentralized right stellate ganglion was tested in anaesthetized spinal cats. These peptides are present in the stellate ganglion and may mediate the stellate ganglion cell excitation underlying a previously described slow cardioacceleration evoked by preganglionic stimulation during block of cholinergic transmission. NT (Tyr11-NT) at doses of 25-200 micrograms produced increases in heart rate of 10-125 beats/min (bpm) and of slow time course. At the dose of 100 micrograms, NT produced a cardioacceleration of 56 +/- 8.4 bpm (mean +/- SEM, n = 13) with an onset latency of 23 +/- 4 s, a slow rise to peak (rise time 62 +/- 4.5 s), and a half decay of 167 +/- 14 s. A cardioacceleration of comparable magnitude (78 +/- 3.8 bpm) caused by close i.a. administration of acetylcholine (100 micrograms, n = 13) had an onset latency of 2 +/- 1 s, a fast rise to a sharp peak (rise time 3 +/- 1 s), and a half decay of 23 +/- 4 s. The analogues, Phe11-NT and Trp11-NT, as well as the stereoisomer, D-Tyr11-NT, had no effect on heart rate when injected at doses up to 400 micrograms. The NT-evoked cardioacceleration was blocked by propranolol or by section of the inferior cardiac nerve and may therefore be attributed to prolonged excitation of stellate ganglion cells. Administration of hexamethonium and atropine was without effect on the NT response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardioacceleration produced by close intra-arterial injection of neurotensin into the stellate ganglion of the cat. 245 13

In order to examine hepatic clearance of gastrointestinal regulatory peptides, rat livers were perfused in situ, and radiolabelled somatostatin (S-14, S-28), gastrin-releasing peptide (GRP-14, GRP-27), and vasoactive intestinal peptide (VIP) were injected into the portal vein and hepatic venous effluent was collected. S-14 and S-28 were not affected significantly by hepatic transit: 91.6 +/- 2.8% (SEM) of S-14 and 95.9 +/- 2.2% of S-28 were recovered, and neither peptide was degraded by hepatic transit, as determined by immunoprecipitation and gel chromatography. GRP-14 and GRP-27 were also not affected by hepatic transit: 91.5 +/- 1.6% of GRP-14 and 94.4 +/- 2.4% of GRP-27 were recovered intact. In contrast, when radiolabelled VIP was infused into the portal vein, 56.7 +/- 7.4% of injected labelled VIP appeared in the hepatic venous effluent, of which only 33.5 +/- 1.2% was intact peptide. Results of these studies indicate that enteric VIP released into the splanchnic/portal circulation is cleared by hepatic transit. However, somatostatin and GRP peptides appear to traverse the liver intact and could potentially produce systemic biological effects.
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PMID:Hepatic clearance of somatostatin and gastrin-releasing peptide. 288 Feb 71

In two studies vasoactive intestinal peptide (VIP) was administered intravenously to two groups of eight in-patient volunteers recovering from severe acute asthma. VIP (6 pmol/kg/min) infusion caused significant (p less than 0.01) increase in peak expiratory flow rate (PEFR) of 26 +/- 9 (SEM) l/min after 30 minutes infusion compared with a bronchodilation of 39 +/- 19 l/min seen with salbutamol (5 mcg/min). Following pretreatment with nebulized ipratropium bromide, VIP infusion caused a significant (p less than 0.02) bronchodilation of 25 l/min. VIP is a bronchodilator in severe asthma, although its effects are less than conventional medication. Reflex mechanisms are unlikely to explain the bronchodilatory effect of intravenous VIP.
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PMID:Vasoactive intestinal peptide as a bronchodilator in severe asthma. 352 52

The distribution of regulatory peptides was studied by radioimmunoassay in the separated mucosa, submucosa and muscularis externa of the human oxyntic stomach, antrum and duodenum. Immunoreactive gastrin, secretin, gastric inhibitory polypeptide and motilin were virtually confined to the mucosa and duodenal submucosa, where endocrine cells are present. Only minor amounts of motilin and gastrin (3.2 +/- 0.5% and 4.3 +/- 0.8% of their total content, means + SEM, respectively) were found in the separated duodenal muscle. Somatostatin-, vasoactive intestinal polypeptide-, substance P-, and mammalian bombesin-like peptides showed distinct differential distributions in all layers. Substance P was low in the stomach and markedly increased in the duodenum, especially in the mucosa (fundus 0.8 +/- 0.2 pmol/g, duodenum 66 +/- 12). Vasoactive intestinal polypeptide and somatostatin, although well represented in the stomach, also increased in the duodenum in all layers of the wall (whole fundus 281 +/- 33 and 334 +/- 46 pmol/g, antrum 124 +/- 18 and 426 +/- 59, duodenum 507 +/- 99 and 1816 +/- 149, respectively). Mammalian bombesin immunoreactivity was comparatively abundant in the oxyntic stomach (mucosa 34 +/- 4.5 pmol/g, muscularis externa 29 +/- 4.8), less so in the antrum (6.3 +/- 1.5 and 11 +/- 3.2 pmol/g, respectively). Low concentrations of this peptide were measured in the duodenum, practically confined to the muscle (this layer 5.1 +/- 1.5 pmol/g, or 83 +/- 5.6% of the total content).
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PMID:Intramural distribution of regulatory peptides in the human stomach and duodenum. 359 62

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


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