Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptide YY (PYY), found in intestinal endocrine cells, and neuropeptide Y (NPY), a structural analogue of PYY found in neurons, inhibit gastric, pancreatic, and intestinal fluid and electrolyte secretion. We examined the effects of these peptides on dispersed chief cells from guinea pig stomach. PYY and NPY, but not pancreatic polypeptide, starting at nanomolar concentrations, caused a 40-50% inhibition of secretin-, vasoactive intestinal polypeptide-, prostaglandin E2-, and forskolin-induced increases in chief cell adenosine 3',5'-cyclic monophosphate (cAMP) content and pepsinogen secretion. These inhibitory peptides did not alter pepsinogen secretion caused by cholecystokinin, carbamylcholine, A23187, 8-bromo-cAMP, or a phorbol ester. The inhibitory effects of PYY on chief cell cAMP production occurred within 30 s, were independent of phosphodiesterase activity, and did not affect the actions of cholera toxin. However, the inhibitory effects of PYY were abolished when chief cells were preincubated with pertussis toxin, an agent that uncouples inhibitory guanine nucleotide binding (G) proteins from their receptors. In gastric chief cells, PYY and NPY attenuate the stimulatory effects of secretagogues whose actions are mediated by changes in cellular levels of cAMP. PYY-induced attenuation of chief cell adenylate cyclase activity appears to involve activation of inhibitory G proteins.
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PMID:Actions of peptide YY and neuropeptide Y on chief cells from guinea pig stomach. 164 73

The pathway by which peptide YY inhibits upper gastrointestinal motility is largely unknown and prompted this investigation. Muscle tension and [3H]acetylcholine release studies were performed on isolated muscle strips and slices obtained from the guinea pig stomach. Peptide YY [0.1-1000 nmol/L; concentration of half-maximal effect (EC50), 6 nmol/L] caused concentration-dependent relaxation of longitudinally oriented muscle strips that was unaffected by hexamethonium but was blocked by atropine and tetrodotoxin, suggesting that the peptide inhibited postganglionic cholinergic neurotransmission. In addition, peptide YY (1 mumol/L) reduced by 42% +/- 6% electrically stimulated muscle contractions that were blocked by atropine and tetrodotoxin, providing additional evidence that the peptide inhibits release of acetylcholine. Next, the effect of peptide YY on potassium-evoked release of [3H]acetylcholine and whether the peptide inhibits cyclic adenosine monophosphate-dependent release of acetylcholine were examined. Peptide YY (1 mumol/L) inhibited KCl (35 mmol/L)-evoked release of [3H]acetylcholine by 58% +/- 6%. The inhibitory action of peptide YY was unaffected by antagonists for dopamine-2, alpha-2, and opiate receptors that are known to mediate presynaptic inhibition. In addition, peptide YY reduced half-maximal forskolin and cholera toxin-evoked release of acetylcholine by 45% +/- 6% and 42% +/- 8%, respectively, suggesting that the peptide can inhibit cyclic adenosine monophosphate-dependent release of acetylcholine. This effect of peptide YY was reversed by pertussis toxin which prevents activation of the inhibitory guanine nucleotide binding protein coupled to adenylate cyclase. In summary, peptide YY inhibited basal and stimulated cholinergic neurotransmission in the guinea pig stomach. In addition, peptide YY antagonized cyclic adenosine monophosphate-mediated release of acetylcholine through a pertussis toxin-sensitive mechanism.
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PMID:Mechanism of action of peptide YY to inhibit gastric motility. 184 99

Incubation of dispersed adenohypophyseal cells from intact male rats with Neuropeptide Y (NPY) or Peptide YY (YY) at 21 degrees C increased maximal 125I LHRHa binding (Bmax) by about 50%. In presence of 10(-7) M NPY, Bmax calculated from saturation isotherm curves was 15.3 +/- 1.9 fmoles x mg-1 proteins, as compared to 10 +/- 1 fmoles x mg-1 in control incubates. The increase was dose dependent with an EC50 of 6.3 +/- 1.8 10(-10) M NPY. Preincubation of the cells with pertussis toxin (PT, 15 ng/ml) for 24 h abolished the effect, suggesting coupling of NPY receptors to G alpha o or G alpha i proteins. NPY 10(-7) M inhibited basal and Forskolin 10(-5) M stimulated intracellular cyclic AMP formation by 31.9 +/- 3.4% and 30.6 +/- 2.3% respectively. Desensitization of protein kinase C by overnight preincubation of the cells with 10(-6) M phorbol ester (PMA) did not interfere with the effect of NPY. In contrast, W7, a calmodulin inhibitor, as well as H7, a protein kinase C inhibitor with a relatively wide spectrum, suppressed the effect of NPY with IC50 of 1.4 +/- 0.6 10(-6) M and 2.2 +/- 0.5 10(-5) M, respectively. Taken together, these results suggest that NPY is able to control unmasking of a cryptic LHRH receptor pool in pituitary cells by a process dependent upon both GTP binding proteins and calmodulin dependent protein kinase.
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PMID:Neuropeptide Y enhances LHRH binding to rat gonadotrophs in primary culture. 817 May 23

Peptide YY (PYY)-preferring receptors are expressed in the renal proximal tubule cell clone Cl.10 isolated from the PKSV-PCT cell line. They mediate PYY-inhibited cAMP production through coupling with pertussis-sensitive Gi proteins. Previous G alpha i RNA antisense experiments demonstrated the exclusive coupling of the PYY receptor to the Gi2 protein. Here we characterized a clone stably expressing G alpha i2 antisense RNA which exhibited only a partial decrease in G alpha i2 content (#60%) as estimated by Western blot. When compared to control Cl.10 cells, this clone, referred to as Cl.10(t), exhibited: (i) an increase in the dissociation constant of PYY receptors (6.42 vs 0.63 nM); (ii) a complete absence of inhibition of [125I]PYY binding by GTP gamma S and GTP; (iii) the failure of PYY to inhibit basal and forskolin-stimulated cAMP levels; (iv) the failure of PYY to stimulate [35S]GTP gamma S binding to membranes. These findings show that partial knockdown of G alpha i2 expression in Cl.10 cells completely abolish the coupling of PYY receptors to biological response.
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PMID:Partial knockdown of G alpha i2 protein is sufficient to abolish the coupling of PYY receptors to biological response in renal proximal tubule cells. 876 88

Neuropeptide Y (NPY) regulates cardiovascular function, smooth muscle contraction and smooth muscle cell proliferation. Stimulation of NPY Y1 and Y2 receptor subtypes has been shown to result in increases in second messengers, such as cytosolic calcium concentrations, which precede physiological events such as cell contraction. To assess whether NPY receptors also stimulate second messengers which may precede mitogenic effects, we measured the mitogen-activated protein kinase (MAPK) activity in NPY receptor-expressing cell lines in response to NPY. CHO K1 cells stably expressing either NPY Y1 or Y2 receptors were shown to specifically bind radiolabelled Peptide YY (PYY), and MAPK activity in these cells was assessed using a peptide kinase assay. NPY stimulated dose-dependent increases in MAPK activity in both NPY Y1 and Y2 receptor-expressing cell lines. The NPY-stimulated MAPK activity was sensitive to pretreatment with pertussis toxin, the MAPK specific inhibitor PD098059 or wortmannin, an inhibitor of phosphatidylinositol-3-kinase (PI-3-K). These results indicate that both NPY Y1 and Y2 receptors stimulate wortmannin-sensitive increases in MAPK activity via Gi proteins and suggest a role for NPY Y1 and Y2 receptors in the regulation of smooth muscle cell growth involved in hypertrophy.
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PMID:Neuropeptide Y Y1 and Y2 receptor-mediated stimulation of mitogen-activated protein kinase activity. 980 11

Neuropeptide Y (NPY) has been shown to inhibit insulin secretion from the islets of Langerhans. We show that insulin secretion in the insulinoma cell line RIN 5AH is inhibited by NPY. 125I-Peptide YY (PYY) saturation and competition-binding studies using NPY fragments and analogues on membranes prepared from this cell line show the presence of a single class of NPY receptor with a Y1 receptor subtype-like profile. Inhibition of insulin secretion in this cell line by NPY fragments and analogues also shows a Y1 receptor-like profile. Both receptor binding and inhibition of insulin secretion showed the same orders of potency with NPY > [Pro34]-NPY > NPY 3-36 >> NPY 13-36. The Y1 receptor antagonist, BIBP 3226, blocks NPY inhibition of insulin secretion from, and inhibits 125I-PYY binding to, RIN 5AH cells. Northern blot analysis using a Y1-receptor specific probe shows that NPY Y1 receptors are expressed by RIN 5AH cells. Y5 receptors are not expressed in this cell line. Neuropeptide Y inhibition of insulin secretion is blocked by incubation with pertussis toxin, implying that the effect is via a G-protein (Gi or Go) coupled receptor. Neuropeptide Y inhibits the activation of adenylyl cyclase by isoprenaline in RIN 5AH cell lysates, and the stimulation of cAMP by glucagon-like peptide-1 (7-36) amide (GLP-1). It also blocks insulin secretion stimulated by GLP-1, but not by dibutyryl cyclic AMP. Hence, we suggest that NPY inhibits insulin secretion from RIN 5AH cells via a Y1 receptor linked through Gi to the inhibition of adenylyl cyclase.
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PMID:Inhibition of glucose stimulated insulin secretion by neuropeptide Y is mediated via the Y1 receptor and inhibition of adenylyl cyclase in RIN 5AH rat insulinoma cells. 986 16

Peptide YY (PYY) released postprandially from the ileum and colon displays a potent inhibition of cephalic and gastric phases of gastric acid secretion through both central and peripheral mechanisms. To modulate vagal regulation of gastric functions, circulating PYY enters the brain through the area postrema and the nucleus of the solitary tract, where it exerts a stimulatory action through PYY-preferring Y1-like receptors, and an inhibitory action through Y2 receptors. In the gastric mucosa, PYY binds to Y1 receptors in the enterochromaffin-like cells to inhibit gastrin-stimulated histamine release and calcium signaling via a pertussis toxin-sensitive pathway.
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PMID:Central and peripheral regulation of gastric acid secretion by peptide YY. 1182 49

In absence of receptor cycling, human/rat neuropeptide Y was found to persistently occupy the guinea pig neuropeptide Y Y1 receptors expressed on the surface of Chinese hamster ovary (CHO) cells (IC50 approximately 8 nM); a lasting occupancy was also evident with active receptor cycling. A similar blockade was obtained with the human neuropeptide Y Y1 receptor (in CHO or SK-N-MC cells). Peptidic antagonists GR238118 (1229U91) and VD-11 blocked the Y1 receptor in the same molarity range. A neuropeptide Y-related Y1 agonist, (Leu31Pro34) human neuropeptide Y, also strongly adhered to the Y1 site. Similar blockade-like occupancy by neuropeptide Y was found with particulates from Y1-expressing CHO cells, and with native neuropeptide Y Y1 receptors of rat synaptosomes. Peptide YY and a related Y1-selective agonist, (Leu31Pro34) human peptide YY, showed a much less stable binding to the neuropeptide Y Y1 receptor with either the intact cells or particulates. The Y1 binding of neuropeptide Y was also less sensitive to chaotropic agents and guanine nucleotides than the binding of peptide YY, indicating a larger stability for association of neuropeptide Y with the receptor. Inhibition of forskolin-stimulated adenylyl cyclase showed a distinctly attenuating agonism for neuropeptide Y, with an activity similar to peptide YY below 1 nM, but considerably lower above 3 nM of the peptides. This activity was largely exerted via pertussis toxin-sensitive G-proteins of Y1-CHO cells. Our findings indicate that signaling by neuropeptide Y via its Y1 receptor could be self-restricting at higher levels of the peptide, in relation to a strong association of the agonist with the Y1 binding site.
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PMID:Neuropeptide Y as a partial agonist of the Y1 receptor. 1629 44

The present study was undertaken to determine whether neuropeptide Y (NPY) induces proliferation of rat aortic endothelial cells (RAECs). Since NPY increased the permeability of RAEC monolayers to large molecules via the NPY Y(3) receptor, RAEC proliferation has been evaluated in terms of NPY-receptor subtypes and also intracellular mechanisms. RAECs were incubated with gases containing 20, 15, or 10% O(2) and a certain amount of N(2), depending on the O(2) content in 5% CO(2) incubators. NPY (10(-9)-10(-6) M) increased the RAEC numbers under hypoxic conditions, such as 15 or 10% O(2). Peptide YY elicited no proliferative effect on RAEC, and NPY-(18-36) inhibited the NPY-induced increase in cell number, suggesting that NPY increases the RAEC count through the NPY Y(3) receptor. Pertussis toxin, U-73122, GF-109203X, myristorylated autocamtide-2-related inhibitory peptide, and wortmannin inhibited the NPY-induced proliferation of RAEC concentration dependently. DY9760e little affected the proliferation caused by NPY. ML-9 and imatinib actually enhanced the NPY-induced proliferation of cells. These results indicated that the NPY Y(3) receptor is coupled with G(i) protein, and that NPY-induced increases in RAEC proliferation are mediated by phospholipase C-protein kinase C and/or phosphatidylinositol 3-kinase pathways. In intracellular Ca(2+)-calmodulin-dependent pathways, calmodulin-dependent protein kinase II partly participates in the NPY-induced cell proliferation. Regarding the previously reported effect of NPY on the permeability of RAEC monolayers to large molecules, it is probable that protein kinase C and phosphatidylinositol 3-kinase pathways are activated for both permeability and cell proliferation induced by NPY under hypoxia, relevant to new insights into the roles of NPY in ischemia-hypoxia.
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PMID:Possible roles of neuropeptide Y Y3-receptor subtype in rat aortic endothelial cell proliferation under hypoxia, and its specific signal transduction. 1740 Jul 22

Cardiac sympathetic nerves release neuropeptide Y (NPY)1-36, and peptide YY (PYY)1-36 is a circulating peptide; therefore, these PP-fold peptides could affect cardiac fibroblasts (CFs). We examined the effects of NPY1-36 and PYY1-36 on the proliferation of and collagen production ([(3)H]proline incorporation) by CFs isolated from Wistar-Kyoto (WKY) normotensive rats and spontaneously hypertensive rats (SHRs). Experiments were performed with and without sitagliptin, an inhibitor of dipeptidyl peptidase 4 [DPP4; an ectoenzyme that metabolizes NPY1-36 and PYY1-36 (Y1 receptor agonists) to NPY3-36 and PYY3-36 (inactive at Y1 receptors), respectively]. NPY1-36 and PYY1-36, but not NPY3-36 or PYY3-36, stimulated proliferation of CFs, and these effects were more potent than ANG II, enhanced by sitagliptin, blocked by BIBP3226 (Y1 receptor antagonist), and greater in SHR CFs. SHR CF membranes expressed more receptor for activated C kinase (RACK)1 [which scaffolds the Gi/phospholipase C (PLC)/PKC pathway] compared with WKY CF membranes. RACK1 knockdown (short hairpin RNA) and inhibition of Gi (pertussis toxin), PLC (U73122), and PKC (GF109203X) blocked the proliferative effects of NPY1-36. NPY1-36 and PYY1-36 stimulated collagen production more potently than did ANG II, and this was enhanced by sitagliptin and greater in SHR CFs. In conclusion, 1) NPY1-36 and PYY1-36, via the Y1 receptor/Gi/PLC/PKC pathway, activate CFs, and this pathway is enhanced in SHR CFs due to increased localization of RACK1 in membranes; and 2) DPP4 inhibition enhances the effects of NPY1-36 and PYY1-36 on CFs, likely by inhibiting the metabolism of NPY1-36 and PYY1-36. The implications are that endogenous NPY1-36 and PYY1-36 could adversely affect cardiac structure/function by activating CFs, and this may be exacerbated in genetic hypertension and by DPP4 inhibitors.
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PMID:NPY1-36 and PYY1-36 activate cardiac fibroblasts: an effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4. 2637 Nov 60


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