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Sökning: L773:0167 0115

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1.
  • Cervin, Anders (författare)
  • Neuropeptide Y 16-36 inhibits mucociliary activity but does not affect blood flow in the rabbit maxillary sinus in vivo
  • 1992
  • Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 39:2-3, s. 237-246
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent investigations have shown neuropeptide Y (NPY) to be present in the rabbit maxillary sinus, and NPY is known to be released upon sympathetic nerve stimulation. To study, in vivo, the effect on mucociliary activity and blood flow, NPY 1-36 and some of its analogues were injected intra-arterially. The effects of the Y1/Y2 agonist NPY 1-36 was compared with the ones of the Y2 agonist NPY 16-36, the Y1-agonist [Leu31,Pro34]NPY and the Y1/Y2 agonist peptide YY. Mucociliary response was recorded photoelectrically and expressed as a percentage of the basal mucociliary activity immediately prior to challenge. The effect on blood flow was measured with laser Doppler flowmetry and expressed as a percentage of the mean blood flow during the 60 s preceding challenge. NPY 1-36 and NPY 16-36 both reduced mucociliary activity dose-dependently at equimolar dosages (0.024-1.2 nmol/kg). The greatest effect was seen after the highest dosage tested. NPY 1-36 reduced mucociliary activity by 14.6 +/- 1.8%, and NPY 16-36 by 13.2 +/- 1.4%. At the highest dosage tested the Y1 receptor agonist [Leu31,Pro34]NPY did not significantly reduce mucociliary activity, whereas PYY reduced mucociliary activity by 15.0 +/- 1.8%. Injections of NPY 16-36 had no effect on blood flow whereas NPY 1-36, [Leu31,Pro34]NPY and PYY all reduced blood flow dose-dependently. Maximal decrease was seen at the highest dosage tested and was 47.1 +/- 5.4%, 70.4 +/- 7.4% and 58.2 +/- 8.4%, respectively. These findings suggest the mucociliary effects to be mediated via Y2 receptors whereas blood flow is regulated via Y1 receptors.
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2.
  • Duan, R D, et al. (författare)
  • Stimulatory effects of human pancreatic polypeptide on rat pancreatic acini
  • 1985
  • Ingår i: Regulatory Peptides. - 0167-0115. ; 12:3, s. 215-222
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of human pancreatic polypeptide (HPP) on rat pancreatic acini has been studied. It was found that HPP stimulated amylase and lipase release from the acini. The secretory response of acini to HPP was dose-dependent in a sigmoidal fashion. Between 10(-9) M and 10(-8) M concentration of HPP there was a slow increase of enzyme release to about 40-60% over basal release. At concentrations of HPP above 10(-8) M there was a rapid increase of enzyme release, amounting to 4-6 times over basal release at 10(-6) M concentration of HPP. The potency of HPP compared to other secretagogues at 10(-7) M concentration was 45% of CCK, 60% of carbachol and 75% of secretin. HPP did not inhibit the effect of CCK, secretin and carbachol on amylase release. The amylase release stimulated by HPP was accompanied by an increase in 45Ca2+ efflux. Atropine or dibutyryl cyclic GMP did not influence the effect of HPP. It is concluded that HPP stimulates the release of enzymes from rat pancreatic acini and that Ca2+ may be a mediator for this secretion.
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3.
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4.
  • Grundemar, L, et al. (författare)
  • Neuropeptide Y : prejunctional inhibition of vagally induced contractions in the guinea pig trachea
  • 1988
  • Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115. ; 23:3, s. 309-313
  • Tidskriftsartikel (refereegranskat)abstract
    • The effects of neuropeptide Y (NPY) on the contractile response to vagus nerve stimulation at different frequencies was studied in an isolated tracheal tube preparation from guinea pig. NPY had no effect on basal smooth muscle tension or on the contractile effect of carbachol, but inhibited vagally induced contractions in a concentration-dependent manner with a greater inhibition at low frequencies than at high. We suggest that the effect is exerted prejunctionally.
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5.
  • Grundemar, L, et al. (författare)
  • Neuropeptide Y suppresses the neurogenic inflammatory response in the rabbit eye; mode of action
  • 1993
  • Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115. ; 43:1-2, s. 57-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Ocular injury in the rabbit causes miosis and breakdown of the blood aqueous barrier (aqueous flare response, AFR), reflecting a sensory nerve-mediated inflammatory response, elicited by the release of tachykinins and calcitonin gene-related peptide (CGRP) from C-fibers. Neuropeptide Y (NPY) occurs in sympathetic fibers in the eye. The study was designed to examine whether NPY and related peptides interfere with the inflammatory response to ocular injury in the rabbit in vivo. The isolated rabbit iris was studied with respect to NPY binding sites and second messenger coupling. The AFR and the miotic response to a standardized injury (infrared irradiation (IR) of the iris) were suppressed dose-dependently by NPY (0.01-1.0 nmol) injected intravitreally 30 min prior the trauma. The treated eye was compared with the contralateral eye, which received 0.9% saline and IR. The Y1 receptor agonist [Pro34]NPY, the Y2 receptor agonist NPY 13-36 and the structurally related peptide YY (1 nmol each) suppressed the AFR in response to IR. Injection of either NPY or the Y1 and Y2 receptor agonists (0.3 nmol each) suppressed the AFR evoked by exogenously applied CGRP (0.15 nmol). Saturation studies with 125I-NPY revealed both high and 'moderate' affinity binding sites in the iris. The Bmax values were 26 and 321 fmol/mg protein, respectively. NPY suppressed the forskolin-stimulated adenylate cyclase activity (IC50 value 19 nM). NPY did not affect basal or noradrenaline-induced accumulation of inositol phosphates in the iris. In conclusion, the rabbit iris seems to be rich in NPY receptors linked to inhibition of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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6.
  • Grundemar, L, et al. (författare)
  • Unlike VIP, the VIP-related peptides PACAP, helodermin and helospectin suppress electrically evoked contractions of rat vas deferens
  • 1992
  • Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115. ; 40:3, s. 331-337
  • Tidskriftsartikel (refereegranskat)abstract
    • We have compared the effects of vasoactive intestinal peptide (VIP) and of the VIP-related peptides pituitary adenylate cyclase activating peptide (PACAP) 1-27 and 1-38, helodermin, helospectin I and helospectin II, on the electrically evoked twitches in the isolated vas deferens of the rat. While VIP was virtually without effect, PACAP 1-38 suppressed the electrically evoked twitches effectively and in a concentration-dependent manner (pIC50 value 7.5). The naturally occurring N-terminal fragment PACAP 1-27 was less effective than PACAP 1-38 (Imax values 37.2% suppression compared to 76.5%) and less potent. The C-terminal fragment PACAP 16-38 was virtually inactive. Also helodermin and helospectin I+II suppressed the electrically evoked twitches effectively and in a concentration-dependent manner (pIC50 values 6.9; 7.2; 6.8, respectively). The three peptides produced similar maximum reduction of the twitches (74-80%). The findings suggest that PACAP, helodermin and helospectin suppress the electrically evoked contractions in the rat vas deferens via receptors distinct from VIP receptors.
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7.
  • Hellstrand, Per, et al. (författare)
  • Role of vasoactive intestinal polypeptide (VIP) in the neurogenic vasodilatation of the portal vein in the rabbit
  • 1985
  • Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 12:4, s. 309-316
  • Tidskriftsartikel (refereegranskat)abstract
    • A coarse network of nerve fibres displaying immunoreactivity for vasoactive intestinal polypeptide (VIP) was found in the wall of the hepatic portal vein of the rabbit. Electrical field stimulation of the rabbit portal vein in vitro, in the presence of adrenergic and cholinergic blockade, caused a marked relaxation of the vessel and a release of VIP into the perfusate. Addition of VIP to the tissue bath elicited a concentration-dependent inhibition of the mechanical activity of the portal vein. The results suggest that VIP containing neurones might participate in the non-cholinergic, non-adrenergic vasodilatation of the portal vein in the rabbit.
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8.
  • Nilsson, Christer, et al. (författare)
  • Distribution of peptidergic nerves in the choroid plexus, focusing on coexistence of neuropeptide Y, vasoactive intestinal polypeptide and peptide histidine isoleucine
  • 1990
  • Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 27:1, s. 11-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Choroid plexus from rat, guinea-pig, rabbit and pig was investigated by light-microscopic immunohistochemistry and by radioimmunoassay for the presence of neuropeptides. A moderately dense supply of nerve fibers containing neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), respectively, was found around blood vessels and in close relation to the secretory epithelium in both pig and rabbit, while lower densities of nerve fibers were found in rat and guinea-pig. Peptide concentrations ranged from 10-40 pmolequivalents/g (pmoleqv/g) for NPY and 0.5-6 pmoleqv/g for VIP in all four species. Peptide histidine isoleucine (PHI) immunoreactive nerve fibers were present in pig choroid plexus at a lower density than NPY and VIP but with a similar distribution. Low concentrations of substance P (0.3-3 pmoleqv/g) and calcitonin gene-related peptide (0.1-3 pmoleqv/g) were found to a varying degree in choroid plexus tissue from the different species, while immunohistochemical investigation was unable to detect any immunoreactive nerve fibers. NPY was often found to coexist with VIP and PHI in pig choroid plexus, while a lesser amount of nerve fibers showed coexistence of NPY and the noradrenaline synthetizing enzyme, dopamine-beta-hydroxylase. Surgical sympathetic denervation by excision of the superior cervical ganglion in the rabbit abolished NPY-containing nerve fibers, as revealed by immunohistochemistry, but only decreased NPY levels by one third, which may be due to different identity of the peptide being detected by the two techniques. It is concluded that NPY-containing nerve fibers have a dual origin in the choroid plexus and coexist with either noradrenaline or VIP/PHI.
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9.
  • Nilsson, Isabelle, 1971-, et al. (författare)
  • Pharmacological analysis of CCK2 receptor ligands using COS-7 and SK-N-MC cells, expressing the human CCK2 receptor
  • 2002
  • Ingår i: Regulatory Peptides. - 1873-1686 .- 0167-0115. ; 103:1, s. 29-37
  • Tidskriftsartikel (refereegranskat)abstract
    • A series of CCK2 receptor ligands were analysed with respect to their interaction with binding sites in the membranes of COS-7 cells and SK-N-MC cells transiently expressing the human CCK2 receptor (short isoform). The ligands were YF476, YM022, AG041R, L-740,093, JB93182, PD134308, and PD136450. Their binding was analysed by radioligand competition using [H-3]L-365,260 as the labelled ligand. Saturation binding analysis indicated that [H-3]L-365,260 interacted with a single class of binding sites. In competition binding experiments using COS-7-cell membranes, all seven ligands were incubated together with 2 nM [H-3]L-365,260. The data for four of the compounds fitted a one-site model (pK(i) values: YM022: 9.2 +/- 0.02, YF476: 9.6 +/- 0.04; L-740,093: 9.2 +/- 0.01, and AG041R: 8.3 +/- 0.06), while the data for the three others fitted a two-site model (pK(i) values: JB93182: 8.8 +/- 0.04 and 6.0 +/- 0.15; PD 134308: 9.0 +/- 0.04 and 6.1 +/- 0.15; and PD 136450: 9.0 +/- 0.02 and 5.4 +/- 0.41). SK-N-MC cell membranes and 2 nM [H-3]L-365,260 were incubated together with YM022, YF476, JB93182, and PD134308. The data for YM022 and YF476 fitted a one-site model (pKi values: YM022: 9.3 +/- 0.06, YF476: 9.4 +/- 0.02), while the data for JB93182 and PD134308 fitted a two-site model (pK(i) values: JB93182: 8.7 +/- 0.06 and 6.2 +/- 0.06; PD134308: 9.1 +/- 0.06 and 7.0 +/- 0.17). Competition binding experiments in the presence of the GTP-analogue guanylylimidodiphosphate, using either of the two cell types, produced similar binding data for PD 134308 and JB93182 as in the absence of GTP-analogue. The human receptor seems to exist in a low and/or high affinity state. The shift from low to high affinity does not seem to reflect the degree of G protein coupling.
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10.
  • Portela-Gomes, GM, et al. (författare)
  • PACAP is expressed in secretory granules of insulin and glucagon cells in human and rodent pancreas - Evidence for generation of cAMP compartments uncoupled from hormone release in diabetic islets
  • 2003
  • Ingår i: Regulatory Peptides. - 1873-1686 .- 0167-0115. ; 113, s. 31-
  • Tidskriftsartikel (refereegranskat)abstract
    • Pituitary adenylate cyclase-activating polypeptide (PACAP) is an islet neuropeptide with potent insulinotropic action. The current study investigates PACAP expression in normal human and rat pancreatic islets, and whether it is altered in diabetic state. To that end, PACAP immunoreactivity was studied by immunofluorescence methods enhanced by the catalyzed reporter deposition (CARD) technique. Insulin and cyclic adenosine monophosphate (cAMP) generation induced by PACAP were investigated in islets isolated from the spontaneously diabetic Goto-Kakizaki (GK) rat. PACAP immunoreactivity was observed in virtually all insulin and glucagon cells in both species, but not in somatostatin or pancreatic polypeptide (PP) cells; this co-localization pattern was unaltered in diabetic pancreata. In normal human pancreas, PACAP was further localized ultrastructurally to the secretory granules of insulin and glucagon cells. PACAP significantly potentiated glucose-stimulated insulin release in isolated islets of normal but not of GK rats. PACAP failed to enhance cAMP generation in normal islets, but induced similar to 5-folds exaggeration in the diabetic islets. In conclusion, using improved immunocytochemistry techniques and electron microscopy (EM), PACAP was shown to be expressed both in normal and diabetic islet cells and localized to secretory granules of insulin and glucagon cells. Furthermore, the insulinotropic action of PACAP was markedly impaired in diabetic islets in spite of exaggerated cAMP response. (C) 2003 Elsevier Science B.V. All rights reserved.
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