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Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms

Grundemar, L LU and Håkanson, R LU (1993) In General Pharamacology 24(4). p.785-796
Abstract

1. Neuropeptide Y (NPY) occurs in both the central and peripheral nervous system. In the periphery, NPY coexists with noradrenaline (NA) in perivascular sympathetic fibers. 2. NPY has a vasopressor effect, reflecting direct vasoconstriction of blood vessels and potentiation of the NA-evoked response. NPY also suppresses the release of NA from sympathetic fibers. 3. The post- and pre-junctional NPY receptors are referred to as Y1 and Y2, respectively. They recognize not only NPY but also the homologous gut hormone peptide YY (PYY). 4. The Y1 and Y2 receptors have been characterized in numerous test systems using analogs of NPY/PYY. Already the deletion of the first N-terminal amino acid (NPY 2-36) results in a marked loss of potency at... (More)

1. Neuropeptide Y (NPY) occurs in both the central and peripheral nervous system. In the periphery, NPY coexists with noradrenaline (NA) in perivascular sympathetic fibers. 2. NPY has a vasopressor effect, reflecting direct vasoconstriction of blood vessels and potentiation of the NA-evoked response. NPY also suppresses the release of NA from sympathetic fibers. 3. The post- and pre-junctional NPY receptors are referred to as Y1 and Y2, respectively. They recognize not only NPY but also the homologous gut hormone peptide YY (PYY). 4. The Y1 and Y2 receptors have been characterized in numerous test systems using analogs of NPY/PYY. Already the deletion of the first N-terminal amino acid (NPY 2-36) results in a marked loss of potency at the Y1 receptor. The Y2 receptor is much less dependent upon an intact N-terminus, and a wide range of C-terminal NPY fragments retain quite high potency. 5. Recently, yet another NPY receptor, Y3, that is distinct from Y1 and Y2 in that it recognizes PYY poorly, has been demonstrated in the brainstem and in the periphery. 6. Further attempts to characterize the various receptor types have relied on truncated and substituted analogs of NPY/PYY. Although such studies suggest the existence of at least three types of NPY receptors, the lack of antagonists has represented a problem. 7. Since NPY may regulate cardiovascular functions via peripheral and central receptors its physiological and possibly pathophysiological significance has attracted much attention. 8. The responsiveness to NPY seems to be altered in animal models of hypertension and elevated plasma levels of NPY have been found in patients under various conditions of stress and in primary hypertension. A number of studies have suggested that NPY may be a pathogenetic factor behind primary hypertension. 9. Antagonists for the various NPY receptors would be useful for an analysis of which effects of these peptides are physiologically relevant. It is tempting to predict that both agonists and antagonists of the NPY receptors could be useful as drugs, for instance, in the treatment of primary hypertension.

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keywords
Amino Acid Sequence, Animals, Central Nervous System/physiology, Hemodynamics/physiology, Humans, Molecular Sequence Data, Neuropeptide Y/metabolism, Peripheral Nervous System/physiology, Receptors, Neuropeptide Y/metabolism
in
General Pharamacology
volume
24
issue
4
pages
785 - 796
publisher
Elsevier
external identifiers
  • pmid:8224732
  • scopus:0027234651
ISSN
0306-3623
DOI
10.1016/0306-3623(93)90151-m
language
English
LU publication?
yes
id
70bd18c7-3cc8-4747-8841-8054e564e26e
date added to LUP
2019-09-03 14:07:58
date last changed
2024-01-01 18:40:40
@article{70bd18c7-3cc8-4747-8841-8054e564e26e,
  abstract     = {{<p>1. Neuropeptide Y (NPY) occurs in both the central and peripheral nervous system. In the periphery, NPY coexists with noradrenaline (NA) in perivascular sympathetic fibers. 2. NPY has a vasopressor effect, reflecting direct vasoconstriction of blood vessels and potentiation of the NA-evoked response. NPY also suppresses the release of NA from sympathetic fibers. 3. The post- and pre-junctional NPY receptors are referred to as Y1 and Y2, respectively. They recognize not only NPY but also the homologous gut hormone peptide YY (PYY). 4. The Y1 and Y2 receptors have been characterized in numerous test systems using analogs of NPY/PYY. Already the deletion of the first N-terminal amino acid (NPY 2-36) results in a marked loss of potency at the Y1 receptor. The Y2 receptor is much less dependent upon an intact N-terminus, and a wide range of C-terminal NPY fragments retain quite high potency. 5. Recently, yet another NPY receptor, Y3, that is distinct from Y1 and Y2 in that it recognizes PYY poorly, has been demonstrated in the brainstem and in the periphery. 6. Further attempts to characterize the various receptor types have relied on truncated and substituted analogs of NPY/PYY. Although such studies suggest the existence of at least three types of NPY receptors, the lack of antagonists has represented a problem. 7. Since NPY may regulate cardiovascular functions via peripheral and central receptors its physiological and possibly pathophysiological significance has attracted much attention. 8. The responsiveness to NPY seems to be altered in animal models of hypertension and elevated plasma levels of NPY have been found in patients under various conditions of stress and in primary hypertension. A number of studies have suggested that NPY may be a pathogenetic factor behind primary hypertension. 9. Antagonists for the various NPY receptors would be useful for an analysis of which effects of these peptides are physiologically relevant. It is tempting to predict that both agonists and antagonists of the NPY receptors could be useful as drugs, for instance, in the treatment of primary hypertension.</p>}},
  author       = {{Grundemar, L and Håkanson, R}},
  issn         = {{0306-3623}},
  keywords     = {{Amino Acid Sequence; Animals; Central Nervous System/physiology; Hemodynamics/physiology; Humans; Molecular Sequence Data; Neuropeptide Y/metabolism; Peripheral Nervous System/physiology; Receptors, Neuropeptide Y/metabolism}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{785--796}},
  publisher    = {{Elsevier}},
  series       = {{General Pharamacology}},
  title        = {{Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms}},
  url          = {{http://dx.doi.org/10.1016/0306-3623(93)90151-m}},
  doi          = {{10.1016/0306-3623(93)90151-m}},
  volume       = {{24}},
  year         = {{1993}},
}