Recent Developments in Our Understanding of the Physiological Role of PP-Fold Peptide Receptor Subtypes

Berglund, Magnus; Hipskind, Philip A.; Gehlert, Donald R.

doi:10.1177/153537020322800301

Cited by 239 publications

(177 citation statements)

References 302 publications

(292 reference statements)

Supporting

Mentioning

173

Contrasting

Unclassified

Order By: Relevance

“…PYY and PYY (5,28,29). It was postulated that differences in the tertiary structure of both forms likely explain the differences in their ligand binding affinities (28,29).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Chelikani

Haver²,

Reidelberger³

2004

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

We compared the effects of the two molecular forms of the brain-gut peptide YY (PYY), PYY(1-36) and PYY(3-36), on gastric emptying. Unanesthetized rats received 20-min intravenous infusions of rat PYY(1-36) (0, 1.7, 5, 17, 50, 100, 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and rat PYY(3-36) (0, 0.5, 1.7, 5, 17, 50, 100, 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ), either alone or combined, and gastric emptying of saline was measured during the last 10 min of infusion. For comparison, human PYY(3-36) was administered at 0, 17, and 50 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 . Gastric emptying was decreased by 11, 24, 26 and 38% in response to 17, 50, 100, and 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of rat PYY(1-36); by 10, 26, 41, 53, and 57% in response to 5, 17, 50, 100, and 170 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of rat PYY(3-36); and by 35 and 53% in response to 17 and 50 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 of human PYY(3-36), respectively. Estimated ED50s were 470 and 37 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 for rat PYY(1-36) and PYY(3-36), respectively. In general, within an experiment, coadministration of PYY(1-36) and PYY(3-36) inhibited gastric emptying by an amount that was comparable to that produced when either peptide was given alone. We conclude that 1) intravenous infusion of PYY(1-36) and PYY(3-36) each produces a dose-dependent inhibition of gastric emptying in rats, 2) PYY(3-36) is an order of magnitude more potent than PYY(1-36) in inhibiting gastric emptying, 3) human PYY(3-36) and rat PYY(3-36) inhibit gastric emptying similarly, and 4) PYY(1-36) and PYY(3-36) do not appear to interact in an additive or synergistic manner to inhibit gastric emptying. intravenous infusion; dose response; interaction PEPTIDE YY (PYY), neuropeptide Y (NPY), and pancreatic polypeptide (PP) comprise the "PP-fold" family of structurally related brain-gut peptides. PYY is synthesized in the gastrointestinal tract, as well as in the central and peripheral nervous systems. Endocrine cells of the ileum, colon, and rectum provide a major source of PYY (2, 47). PYY has also been detected in gastric mucosa, pancreatic islets, myenteric and serosal ganglia, sympathetic neurons, adrenal gland, spinal cord, and brain, including the hypothalamus, pituitary, pons, medulla oblongata, and the brain stem (7-9, 15, 16, 22, 30, 32, 37).Food intake releases PYY into the circulation (2, 47). Systemic administration of PYY inhibits food intake, gastric emptying, intestinal fluid and electrolyte secretion, gallbladder contraction, and exocrine pancreatic secretion (5, 36). Whether PYY acts physiologically by endocrine, neurocrine, and/or paracrine mechanisms to produce these effects remains to be determined. If PYY acts as a blood-borne hormonal signal to produce an effect, then it is important to determine whether the effect is produced by intravenous doses of PYY that reproduce meal-induced increases in plasma PYY.The two major molecular forms of PYY found in the gut and circulation are PYY(1-36) and PYY(3-36) (19 -21). In humans, plasma concentrations of PYY were reported to be 11 pM in the fasted state with PYY(3-36) contributing 37% ...

show abstract

“…PYY and PYY (5,28,29). It was postulated that differences in the tertiary structure of both forms likely explain the differences in their ligand binding affinities (28,29).…”

Section: Discussionmentioning

confidence: 99%

“…Systemic administration of PYY inhibits food intake, gastric emptying, intestinal fluid and electrolyte secretion, gallbladder contraction, and exocrine pancreatic secretion (5,36). Whether PYY acts physiologically by endocrine, neurocrine, and/or paracrine mechanisms to produce these effects remains to be determined.…”

mentioning

confidence: 99%

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Chelikani

Haver²,

Reidelberger³

2004

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Both PYY and NPY bind to PP-fold receptors called the neuropeptide Y receptors, which are members of the rhodopsin-like receptor family belonging to the heterogeneous superfamily of G protein-coupled receptors. Five subtypes of Y receptors have been cloned from mammals (Y1, Y2, Y4, Y5, and Y6) (23). PYY and NPY have similar binding affinity compared to the Y1, Y2, and Y5 receptors (23)(24)(25)(26), which likely contributes to the sharing of several biological functions, including inhibition of gastrointestinal motility, chloride ion secretion, and pancreatic enzyme secretion.…”

mentioning

confidence: 99%

Peptide YY and Neuropeptide Y Induce Villin Expression, Reduce Adhesion, and Enhance Migration in Small Intestinal Cells through the Regulation of CD63, Matrix Metalloproteinase-3, and Cdc42 Activity

Lee

Hadi

Halldén

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Peptide YY (PYY) and neuropeptide Y (NPY) are regulatory peptides synthesized in the intestine and brain, respectively, that modify physiological functions affecting nutrient assimilation and feeding behavior. Because PYY and NPY also alter the expression of intestine-specific differentiation marker proteins and the tetraspanin CD63, which is involved in cell adhesion, we investigated whether intestinal cell differentiation could be linked to mucosal cell adhesion and migration through these peptides. PYY and NPY significantly decreased cell adhesion and increased cell migration in a dose-dependent manner prior to cell confluency in our model system, non-tumorigenic small intestinal hBRIE 380i cells. Both peptides reduced CD63 expression and CD63-dependent cell adhesion. CD63 overexpression increased and antisense CD63 cDNA decreased intestinal cell adhesion. In parallel, both PYY and NPY increased expression of matrix metalloproteinase-3 (MMP-3) to a level sufficient to induce cell migration by activating the Rho GTPase Cdc42. The effects of both peptides on cell migration were blocked in cells constitutively overexpressing dominant-negative Cdc42. PYY and NPY also significantly induced the expression of the differentiation marker villin, which could be eliminated by an MMP inhibitor at a concentration that inhibits cell migration. Increased MMP-3 activity, which enhanced cell migration, also induced villin mRNA levels. Therefore, these data indicate that the alteration of adhesion and migration by PYY and NPY occurs in part by synchronous modulation of three proteins that are involved in extracellular matrix-basolateral membrane interactions, CD63, MMP-3 and Cdc42, and that PYY/NPY regulation of expression of mucosal proteins such as villin is linked to the process of cell migration and adhesion.

show abstract

“…15,16 Importantly, activation of renal sympathetic nerves leads to the release of neuropeptide Y (NPY). 17 NPY is an example of a pancreatic polypeptide (PP)-fold peptide, 18 and NPY binds with high affinity to Y 1 , Y 2 , and Y 5 receptors but not Y 4 receptors, 18 whereas Y 3 receptors most likely do not exist. 19 Both Y 1 and Y 2 receptors are expressed in the kidney, 17,18 whereas Y 5 receptors are expressed predominantly in the central nervous system, not the kidney.…”

mentioning

confidence: 99%

“…17 NPY is an example of a pancreatic polypeptide (PP)-fold peptide, 18 and NPY binds with high affinity to Y 1 , Y 2 , and Y 5 receptors but not Y 4 receptors, 18 whereas Y 3 receptors most likely do not exist. 19 Both Y 1 and Y 2 receptors are expressed in the kidney, 17,18 whereas Y 5 receptors are expressed predominantly in the central nervous system, not the kidney. 20 Because Y 1 and Y 2 receptors coupled to G i 19 exist in the kidney and are stimulated by NPY, it is conceivable that the coinvolvement of the RAS, sympathetic nervous system, and kidney in SHR hypertension is mediated in part by activation of Y 1 and/or Y 2 receptors leading to a potentiation of Ang IIinduced renal vasoconstriction in the SHR kidney.…”

mentioning

confidence: 99%

Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II–Induced Renal Vasoconstriction

Dubinion

Zhu

et al. 2006

Hypertension

View full text Add to dashboard Cite

Abstract-TheKey Words: receptors Ⅲ neuropeptides Ⅲ peptides Ⅲ hypertension T he renin-angiotensin system (RAS) is essential for the development and maintenance of genetic hypertension in spontaneously hypertensive rats (SHRs). 1,2 Moreover, transplantation studies reveal that, in addition to the RAS, the SHR kidney is pivotal to the pathophysiology of hypertension in the SHR. 3,4 Finally, the renal sympathetic nervous system also appears to importantly contribute to the pathophysiology of hypertension in SHRs. In support of this latter concept, chronic denervation of the SHR kidney both delays the development of hypertension and attenuates the maximum increase in blood pressure in SHR. [5][6][7][8] Thus, there appears to be a coinvolvement of the RAS, the sympathetic nervous system, and the kidney in SHR hypertension.Many studies have been performed in search of a possible explanation for the coinvolvement of the RAS and the kidney in SHR hypertension. In this regard, studies do not support an increased expression of renal angiotensin II (Ang II) receptors 9 or increased levels of circulating 10 or renal 11 Ang II; also, SHRs do not have altered renal Ang II degradation rates. 12 However, SHRs do exhibit increased renovascular responses to Ang II, 13,14 and this appears to be the explanation for the coinvolvement of the RAS and the kidney in SHR hypertension.Our previous research indicates that G i mediates, in part, the enhanced renovascular response to Ang II in SHR. For example, pertussis toxin, an inhibitor of G i , abolishes the increased renovascular response to Ang II in SHR. 15,16 Importantly, activation of renal sympathetic nerves leads to the release of neuropeptide Y (NPY). 17 NPY is an example of a pancreatic polypeptide (PP)-fold peptide, 18 and NPY binds with high affinity to Y 1 , Y 2 ,

show abstract

Recent Developments in Our Understanding of the Physiological Role of PP-Fold Peptide Receptor Subtypes

Cited by 239 publications

References 302 publications

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Comparison of the inhibitory effects of PYY(3-36) and PYY(1-36) on gastric emptying in rats

Peptide YY and Neuropeptide Y Induce Villin Expression, Reduce Adhesion, and Enhance Migration in Small Intestinal Cells through the Regulation of CD63, Matrix Metalloproteinase-3, and Cdc42 Activity

Pancreatic Polypeptide-Fold Peptide Receptors and Angiotensin II–Induced Renal Vasoconstriction

Contact Info

Product

Resources

About