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Home / Equine Research Bank / Br J Pharmacol / Heterogeneity of the neuropeptide Y (NPY) contractile and re...
British journal of pharmacology2004; 143(8); 976-986; doi: 10.1038/sj.bjp.0706005

Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries.

Abstract: The distribution of neuropeptide Y (NPY)-immunorective nerves and the receptors involved in the effects of NPY upon electrical field stimulation (EFS)- and noradrenaline (NA)-elicited contractions were investigated in horse penile small arteries. NPY-immunoreactive nerves were widely distributed in the erectile tissues with a particularly high density around penile intracavernous small arteries. In small arteries isolated from the proximal part of the corpora cavernosa, NPY (30 nM) produced a variable modest enhancement of the contractions elicited by both EFS and NA. At the same concentration, the NPY Y(1) receptor agonist, [Leu(31), Pro(34)]NPY, markedly potentiated responses to EFS and NA, whereas the NPY Y(2) receptor agonist, NPY(13-36), enhanced exogenous NA-induced contractions. In arteries precontracted with NA, NPY, peptide YY (PYY), [Leu(31), Pro(34)]NPY and the NPY Y(2) receptor agonists, N-acetyl[Leu(28,31)]NPY (24-36) and NPY(13-36), elicited concentration-dependent contractile responses. Human pancreatic polypeptide (hPP) evoked a biphasic response consisting of a relaxation followed by contraction. NPY(3-36), the compound 1229U91 (Ile-Glu-Pro-Dapa-Tyr-Arg-Leu-Arg-Tyr-NH2, cyclic(2,4')diamide) and eventually NPY(13-36) relaxed penile small arteries. The selective NPY Y(1) receptor antagonist BIBP3226 ((R)-N(2)-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]D-arginineamide) (0.3 microM) shifted to the right the concentration-response curves to both NPY and [Leu(31), Pro(34)]NPY and inhibited the contractions induced by the highest concentrations of hPP but not the relaxations observed at lower doses. In the presence of the selective NPY Y(2) receptor antagonist BIIE0246 ((S)-N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-y1]-1-piperazinyl]-2-oxoethyl]cyclo-pentyl-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2, 4-triazol-4-yl]ethyl]-argininamide) (0.3 microM), the Y(2) receptor agonists NPY(13-36) and N-acetyl[Leu(28,31)]NPY (24-36) evoked potent slow relaxations in NA-precontracted arteries, under conditions of nitric oxide (NO) synthase blockade. Mechanical removal of the endothelium markedly enhanced contractions of NPY on NA-precontracted arteries, whereas blockade of the neuronal voltage-dependent Ca(2+) channels did not alter NPY responses. These results demonstrate that NPY can elicit dual contractile/relaxing responses in penile small arteries through a heterogeneous population of postjunctional NPY receptors. Potentiation of the contractions evoked by NA involve both NPY Y(1) and NPY Y(2) receptors. An NO-independent relaxation probably mediated by an atypical endothelial NPY receptor is also shown and unmasked in the presence of selective antagonists of the NPY contractile receptors.
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Publication Date: 2004-11-22 PubMed ID: 15557288PubMed Central: PMC1575958DOI: 10.1038/sj.bjp.0706005Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates how neuropeptide Y (NPY), a protein involved in various physiological processes, affects small arteries in the horse penis. The study discloses that NPY has both contractile and relaxing effects on these arteries, and these dual responses are mediated through a complex interplay of different NPY receptor types.

Overview of the Study and Methodology

  • The researchers examined the distribution of NPY-reactive nerves and their receptors in horse erectile tissues. They used electrical field stimulation (EFS) and noradrenaline (NA) induced contractions to assess the effects of NPY.
  • NPY-immunoreactive nerves were found to be widely distributed in the erectile tissues, particularly around the penile intracavernous small arteries.
  • The researchers also used different substances that mimic NPY or block its receptors to further investigate how the peptide functions.

Findings of the Study

  • In small arteries from the proximal part of the corpora cavernosa, NPY produced a modest enhancement of contractions induced by both EFS and NA. NPY’s effects varied across the arteries and the magnitude of the contractions induced was not significant.
  • Different types of NPY receptors produced different responses. The NPY Y1 receptor greatly enhanced responses to EFS and NA, while the NPY Y2 receptor only enhanced contractions induced by exogenous NA, an endogenous compound involved in the control of blood pressure.
  • NPY, along with several NPY-like substances and receptor agonists, caused a concentration-dependent contractile response in NA-precontracted arteries. However, the relaxing response was the predominant outcome when using human pancreatic polypeptide (hPP), a protein having similar properties to NPY.

Conclusion and Implications of the Study

  • The researchers concluded that NPY has the capability to elicit both contractile and relaxing responses in penile small arteries. This dual function is mediated by an interplay of different NPY receptors.
  • This insight sheds light on the complex physiological function of NPY and its receptor system. It may also help in understanding the potential therapeutic advances that can be made by manipulating the NPY system, especially in relation to erectile dysfunction.

Cite This Article

APA
Prieto D, Arcos LR, Martínez P, Benedito S, García-Sacristán A, Hernández M. (2004). Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries. Br J Pharmacol, 143(8), 976-986. https://doi.org/10.1038/sj.bjp.0706005

Publication

British journal of pharmacology
ISSN: 0007-1188
NlmUniqueID: 7502536
Country: England
Language: English
Volume: 143
Issue: 8
Pages: 976-986

Researcher Affiliations

Prieto, Dolores
  • Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain. dprieto@farm.ucm.es
Arcos, Luis Rivera de Los
    Martínez, Pilar
      Benedito, Sara
        García-Sacristán, Albino
          Hernández, Medardo

            MeSH Terms

            • Animals
            • Arteries / drug effects
            • Arteries / physiology
            • Dose-Response Relationship, Drug
            • Horses
            • In Vitro Techniques
            • Male
            • Norepinephrine / pharmacology
            • Penis / blood supply
            • Penis / drug effects
            • Penis / physiology
            • Receptors, Neuropeptide Y / physiology
            • Vasoconstriction / drug effects
            • Vasoconstriction / physiology
            • Vasodilation / drug effects
            • Vasodilation / physiology

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            Citations

            This article has been cited 3 times.
            1. Zheng YL, Wang WD, Li MM, Lin S, Lin HL. Updated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis.. Front Cardiovasc Med 2021;8:630968.
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            2. Salazar I, Sánchez-Quinteiro P, Alemañ N, Prieto D. Anatomical, immnunohistochemical and physiological characteristics of the vomeronasal vessels in cows and their possible role in vomeronasal reception.. J Anat 2008 May;212(5):686-96.
              doi: 10.1111/j.1469-7580.2008.00889.xpubmed: 18430091google scholar: lookup
            3. Gradin KA, Buus CL, Li JY, Frøbert O, Simonsen U. Neuropeptide Y2 receptors are involved in enhanced neurogenic vasoconstriction in spontaneously hypertensive rats.. Br J Pharmacol 2006 Jul;148(5):703-13.
              doi: 10.1038/sj.bjp.0706774pubmed: 16715120google scholar: lookup
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